Affinage

DIAPH1

Protein diaphanous homolog 1 · UniProt O60610

Audit flag: ungrounded claim
Length
1272 aa
Mass
141.3 kDa
Annotated
2026-06-09
100 papers in source corpus 52 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DIAPH1 (mDia1) is an autoinhibited Rho-family GTPase effector that nucleates and processively elongates unbranched actin filaments, coordinating the actin and microtubule cytoskeletons to drive cell migration, polarity, division, and immune and vascular signaling (PMID:10559899, PMID:11146620, PMID:14657240). In the resting state, an intramolecular DID-DAD interaction holds the protein inactive; GTP-RhoA binds the regulatory N-terminal domain at a site that overlaps the DAD-binding surface, displacing the DAD and releasing the FH1-FH2 module, as defined by crystal and NMR structures of the dimeric N-terminal armadillo-repeat domain and of an N-terminal/FH2-DAD assembly (PMID:15866170, PMID:20927338). The released FH2 domain dimerizes to nucleate actin, protects barbed ends from capping protein, and elongates filaments processively while undergoing helical rotation around the filament; the FH1 domain recruits profilin-actin and this rotation renders filaments resistant to cofilin severing (PMID:12906795, PMID:14657240, PMID:21148346, PMID:29760064). mDia1 nucleation frequency is tuned directly by free G-actin concentration, and its activity is further modulated by cofactors including Flightless-I, APC, and SPIN90-Arp2/3, the latter coupling linear mDia1 elongation to branched network formation (PMID:18827014, PMID:20223827, PMID:20566685, PMID:32572169). Through these activities mDia1 builds stress fibers downstream of RhoA in balance with ROCK, drives force-induced focal adhesion maturation and mechanosensitive stress-fiber repair, activates serum response factor by depleting the G-actin pool, and aligns microtubules with actin to control cell polarity, MTOC orientation, and focal-adhesion turnover (PMID:10559899, PMID:11402062, PMID:12429848, PMID:16943426, PMID:34822787). It directly binds and engages microtubules through the FH2 domain and acts in formin cascades with INF2 (scaffolded by IQGAP1) and with capping protein to generate stable detyrosinated microtubules (PMID:21998204, PMID:22918941, PMID:27030671). mDia1 also serves as the essential membrane-proximal cytoplasmic effector of RAGE, binding the RAGE cytoplasmic tail to transduce ligand-stimulated AKT signaling, a protein-protein interaction that is pharmacologically tractable and whose inhibition attenuates diabetic complications and vascular neointimal expansion (PMID:22194616, PMID:22511750, PMID:26936329, PMID:34818060). In vivo it is required for T lymphocyte trafficking, NK and macrophage cytoskeletal organization, TCR-driven spatiotemporal LAT phosphorylation, hematopoietic progenitor homeostasis, megakaryocyte proplatelet formation, and male fertility, and is phosphorylated by Cdk1 to restrain profilin binding and cortical tension during metaphase, preventing inappropriate spindle assembly checkpoint activation (PMID:17682067, PMID:17699759, PMID:19427913, PMID:19234535, PMID:25298036, PMID:30816115, PMID:30256801, PMID:31911947). Gain-of-function truncations that delete the DAD constitutively activate DIAPH1, causing increased F-actin and stabilized microtubules, macrothrombocytopenia, and DFNA1 sensorineural hearing loss (PMID:26912466, PMID:27707755).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Established mDia1 as a RhoA effector for actin organization, answering how active RhoA produces distinct actin architectures.

    Evidence Constitutively active and dominant-negative mDia1 constructs with actin imaging, showing mDia1 and ROCK act concurrently downstream of Rho

    PMID:10559899

    Open questions at the time
    • Mechanism of autoinhibition release not yet structurally defined
    • Biochemical actin activity not yet reconstituted
  2. 2001 High

    Defined mDia1 as a mechanosensing effector and a coordinator of actin and microtubules, separating its functions from ROCK/myosin contractility.

    Evidence Force application with live imaging of focal contacts plus FH2 point mutagenesis dissociating microtubule alignment from actin accumulation; spindle localization mapped to an FH3 segment

    PMID:11146620 PMID:11171383 PMID:11402062

    Open questions at the time
    • Molecular basis of FH2-microtubule coordination unresolved
    • Spindle function of mDia1 not yet established
  3. 2002 High

    Connected mDia1 actin assembly to transcription and to Rac crosstalk, answering how a formin influences gene expression and adjacent GTPase activity.

    Evidence SRF reporter with non-polymerizable actin mutant placing actin assembly upstream of SRF; epistasis with Cas/Src/Crk/DOCK180 for Rho-dependent Rac activation

    PMID:12021256 PMID:12429848

    Open questions at the time
    • Direct link between mDia1 and the Rac-activation machinery not biochemically defined
    • In vivo relevance of SRF activation unaddressed
  4. 2003 High

    Reconstituted mDia1 as a processive barbed-end actin nucleator/elongator and showed autoinhibition biochemically, answering its core enzymatic mechanism.

    Evidence Pyrene-actin assays with purified FH1-FH2 and N-terminal constructs, barbed-end capping protection, yeast complementation, plus genetic KO showing Drf3 compensation

    PMID:12676083 PMID:12906795 PMID:14657240

    Open questions at the time
    • Atomic structure of the autoinhibited state not yet solved
    • GDP- vs GTP-RhoA effect on relief incompletely resolved
  5. 2005 High

    Provided the structural basis for RhoA-mediated activation, answering how GTP-RhoA competes with the DAD to relieve autoinhibition.

    Evidence Crystal structure of the dimeric N-terminal DID domain with NMR/biochemical mapping of overlapping RhoA and DAD sites

    PMID:15866170

    Open questions at the time
    • Conformational dynamics of full-length activation not captured
    • FH2 release upon DAD displacement not directly visualized
  6. 2006 Medium

    Showed autoinhibition controls both actin activity and membrane localization, framing dual regulation as a general DRF principle.

    Evidence In vitro actin assays plus localization of GTPase-binding-deficient GFP-mDia1 variants

    PMID:16943183

    Open questions at the time
    • Single-lab study without reconstitution of the localization determinant
    • Membrane receptor mediating localization not identified here
  7. 2007 High

    Established in vivo requirements for mDia1 in immune trafficking and hematopoiesis, and placed it downstream of a Galpha12/13-LARG-RhoA axis for MTOC polarization.

    Evidence mDia1 knockout mice with lymphocyte trafficking, chemotaxis, and hematopoietic phenotyping; Galpha12/13-deficient MEFs with LARG-pericentrin co-IP and MTOC assays

    PMID:17682067 PMID:17699759 PMID:17959834

    Open questions at the time
    • Cell-intrinsic vs systemic contributions to myeloproliferation not fully separated
    • Mechanism linking mDia1 to MTOC orientation incompletely defined
  8. 2008 High

    Defined G-actin concentration as a direct regulator of mDia1 nucleation and identified Memo as upstream of membrane-localized RhoA-mDia1.

    Evidence Single-molecule imaging with latrunculin and modeling; Memo siRNA with RhoA/mDia1 localization imaging in breast carcinoma cells

    PMID:18827014 PMID:18955552

    Open questions at the time
    • Physiological range of G-actin tuning in vivo not established
    • Direct vs indirect Memo-RhoA mechanism not biochemically defined
  9. 2010 High

    Resolved the helical-rotation elongation mechanism and the autoinhibited tetrameric structure, and identified cooperative cofactors (APC, Fli-I) and a Src-trafficking/oncogenic role.

    Evidence Single-molecule fluorescence polarization of elongation; crystal structure of N+C tetramer; in vitro reconstitution with APC-B and Flightless-I; mDia1-KO MEFs with v-Src trafficking and tumor assays; steroidogenic and Golgi imaging

    PMID:20223827 PMID:20566685 PMID:20591975 PMID:20679479 PMID:20927338 PMID:21148346 PMID:21680709

    Open questions at the time
    • How rotation couples to physiological filament functions left open
    • In vivo contribution of APC/Fli-I cofactors unaddressed
    • Src-transport mechanism along actin not molecularly resolved
  10. 2011 High

    Established mDia1 as the essential intracellular effector of RAGE and mapped its microtubule-binding and filopodial partnerships, broadening its receptor and cytoskeletal interactomes.

    Evidence NMR structure of ctRAGE-mDia1 interface with AKT/migration assays; in vitro microtubule co-sedimentation; FRET/RNAi defining CLIP-170, IRSp53, and Rif partnerships

    PMID:19114595 PMID:21339294 PMID:21998204 PMID:22179776 PMID:22194616

    Open questions at the time
    • Downstream signaling chain from ctRAGE-mDia1 to AKT incompletely defined
    • Stoichiometry of simultaneous actin and microtubule engagement in cells unclear
  11. 2012 High

    Linked mDia1 to stable microtubule formation via capping-protein hand-off and to membrane-domain trafficking, plus an in vivo vascular RAGE pathway.

    Evidence RNAi/pharmacology showing capping protein releases mDia1 to act on MTs; Cav1/caveolae trafficking downstream of Abl; mDia1-KO femoral artery injury with c-Src/Rac1/AKT pathway dissection

    PMID:22454521 PMID:22511750 PMID:22918941

    Open questions at the time
    • Direct mDia1-microtubule stabilization step not isolated from actin effects
    • Caveolae regulation mechanism single-lab
  12. 2016 High

    Identified DIAPH1 gain-of-function disease alleles and an mDia1-INF2 formin cascade, and validated the ctRAGE-DIAPH1 interaction as druggable.

    Evidence Patient R1213*/C-terminal truncation studies with knock-in mice (macrothrombocytopenia, DFNA1 hearing loss); siRNA epistasis defining IQGAP1-scaffolded mDia1-INF2; small-molecule competitive inhibitor screen

    PMID:26912466 PMID:26936329 PMID:27030671 PMID:27707755

    Open questions at the time
    • Tissue-specific consequences of constitutive activation incompletely mapped
    • In vivo selectivity of early ctRAGE-DIAPH1 inhibitors not established
  13. 2018 High

    Defined cofilin-resistance via helical rotation, Cdk1 control of mitotic cortical tension, a TGFbeta-receptor endocytic role, and essential function in spermatogenesis.

    Evidence EM/cofilin assays with tethered mDia1; Cdk1 phospho-mutant DIAPH1 with cortical tension and SAC measurements; Diaph1-TbetaRII/Rab5a co-IP with internalization assays; mDia1/3 double-KO superresolution in Sertoli cells

    PMID:29760064 PMID:30256801 PMID:30816115 PMID:32304339

    Open questions at the time
    • Kinase-substrate spatial regulation of Cdk1-DIAPH1 in cells not fully resolved
    • Direct vs scaffold role in TbetaRII endocytosis incompletely separated
  14. 2020 High

    Established mDia1/mDia3 control of TCR-driven LAT phosphorylation and an mDia1-SPIN90-Arp2/3 ternary complex coupling linear and branched actin networks.

    Evidence mDia1/mDia3 KO mice plus SMIFH2 with LAT/Zap70 phospho and IS imaging; in vitro reconstitution and TIRF of the SPIN90-Arp2/3-mDia1 complex

    PMID:31911947 PMID:32572169

    Open questions at the time
    • How formin-built filaments spatially gate LAT phosphorylation unresolved
    • In vivo prevalence of SPIN90-mDia1 cortical filaments not quantified
  15. 2021 High

    Defined force-activated pulsatile mDia1 activity as a stress-fiber safety valve and advanced a structure-guided RAGE-DIAPH1 antagonist for diabetic complications.

    Evidence mDia1 biosensor imaging with laser ablation, traction force microscopy, and modeling; NMR-defined RAGE229 with in vivo streptozotocin diabetic kidney efficacy

    PMID:34818060 PMID:34822787

    Open questions at the time
    • Force-sensing molecular trigger of mDia1 activation not identified
    • Long-term and tissue-broad efficacy/safety of RAGE229 untested here
  16. 2023 Medium

    Extended DIAPH1 function to metabolic regulation via actin-dependent SREBP1 nuclear translocation and lipid synthesis.

    Evidence Ldlr-/- x Diaph1-/- atherosclerosis model with hepatic lipogenic gene expression and SREBP1 nuclear localization imaging

    PMID:36932214

    Open questions at the time
    • Mechanism linking actin dynamics to SREBP1 transport unresolved
    • Single-lab in vivo correlation between actin state and SREBP1 translocation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse upstream activators (RhoA, Rif, RAGE, Memo, force) are integrated to direct mDia1 to specific subcellular sites and substrate cytoskeletons remains unresolved.
  • No unified model of mDia1 spatial targeting across stimuli
  • Quantitative rules governing actin vs microtubule engagement in vivo unknown
  • Selective therapeutic modulation of individual mDia1 functions untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005815 microtubule organizing center 3 GO:0005856 cytoskeleton 3 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
CLIP-170INF2IQGAP1IRSP53PKD2RAGERHOASPIN90
Complex memberships
Hck-WASp-mDia1 complexSPIN90-Arp2/3-mDia1 ternary complexctRAGE-DIAPH1 complexmDia1-INF2-IQGAP1 complex

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 GTP-bound RhoA activates mDia1 by disrupting mDia1's intramolecular autoinhibitory interactions; active mDia1 induces formation of thin actin stress fibers, and mDia1 and ROCK work concurrently downstream of Rho to produce stress fibers of varying thickness and density depending on the balance of the two activities. Constitutively active mDia1 expression, dominant-negative constructs, in vitro binding studies, fluorescence microscopy of actin structures Nature cell biology High 10559899
2001 Constitutively active mDia1 (DeltaN3) is sufficient to restore force-induced focal contact formation in Rho-inhibited cells, demonstrating that mDia1 acts downstream of Rho to mediate mechanosensing-dependent focal contact growth independently of ROCK and myosin II contractility. Micropipette force application, GFP-vinculin/paxillin live imaging, expression of constitutively active mDia1 mutants, C3 transferase Rho inhibition, ROCK and myosin II pharmacological inhibition The Journal of cell biology High 11402062
2001 Active mDia1 (DeltaN3 mutant containing FH1 and FH2 regions) induces bipolar cell elongation and aligns microtubules parallel to F-actin bundles along the long cell axis; point mutations in the FH2 region abolish microtubule alignment but not actin accumulation, revealing that the FH2 domain coordinates microtubules and F-actin. Expression of constitutively active mDia1 mutants, co-expression of dominant-negative FH2 fragment, point mutagenesis, immunofluorescence of microtubules and F-actin in HeLa cells Nature cell biology High 11146620
2001 mDia1 localizes to the mitotic spindle in HeLa cells from prophase to telophase, independently of Rho activity; a 173-amino acid segment in the FH3 region (including Leu434 and Leu455) is necessary and sufficient for spindle localization. Immunocytochemistry with polyclonal anti-mDia1 antibody, mitotic spindle fractionation/western blot, GFP-fusion truncation mutants, point mutagenesis, C3 exoenzyme and Val14RhoA microinjection Journal of cell science High 11171383
2001 mDia1 FH1 domain binds profilin in vitro and in cells; the RBD (Rho-binding domain) complexes with the C-terminal CIID module for autoinhibition; overexpression of the RBD alone causes membrane ruffling and loss of stress fibers, which is suppressed by dominant-negative Rac, indicating that the isolated RBD upregulates Rac activity. In vitro binding assays, transfection of deletion constructs, dominant-negative Rac co-expression, morphological phenotyping Journal of cell science Medium 11707518
2002 mDia1 mediates Rho-dependent Rac activation through a pathway involving Cas phosphorylation (via Src/Crk/DOCK180), and this mDia1 activity is antagonized by ROCK; expression of dominant-negative mDia1 inhibits membrane ruffle formation induced by ROCK inhibition (Y-27632). C3 exoenzyme and Y-27632 pharmacological inhibition, dominant-negative mDia1 expression, N17Rac expression, GTP-Rac pull-down assay, PP1 Src inhibitor, dominant-negative Cas and Crk-II mutants The Journal of cell biology High 12021256
2002 mDia1 activates serum response factor (SRF) by promoting F-actin assembly and depleting the G-actin pool; the FH2 domain (extended C-terminal region) is required for both actin polymerization and SRF activation, placing actin assembly upstream of SRF; the FH1 domain is dispensable for these functions. SRF luciferase reporter assay, actin polymerization assays, non-polymerizable actin mutant (R62D), mDia1 domain deletion constructs Molecular biology of the cell High 12429848
2003 Purified mDia1 FH2-containing constructs are potent actin nucleators in vitro; the FH1 domain is required for nucleation when actin is profilin-bound; an N-terminal mDia1 construct strongly inhibits C-terminal actin nucleation, consistent with autoinhibition; RhoA partially relieves this inhibition regardless of whether it is GDP- or GTP-bound. In vitro pyrene-actin polymerization assay with purified proteins, size exclusion chromatography (multimer analysis), GST-RhoA binding Current biology : CB High 12906795
2003 Purified mDia1 FH2 domain dimerizes and protects growing actin filament barbed ends from capping protein, enabling processive elongation; this mechanism is conserved with yeast Bni1, and dominant-active mDia1 partially complements BNI1 function in yeast. In vitro actin assembly assays, barbed-end capping protection assay, yeast complementation genetics Molecular biology of the cell High 14657240
2003 Genetic disruption of Drf1 (mDia1) reveals compensatory upregulation of Drf3; Drf1-/- cells show fewer actin stress fibers but are more motile with more lamella and filopodia, attributable to Cdc42-mediated Drf3 activation; mDia1 loss-of-function establishes it as required for RhoA-mediated stress fiber formation in primary mouse cells. Homologous recombination gene targeting, Drf3 antibody microinjection, FRET analysis of Cdc42-Drf3 interaction, dominant-negative Drf3 variants Current biology : CB Medium 12676083
2004 mDia1 (Drf1) physically interacts with PKD2 via the cytoplasmic C-terminus of PKD2 and the mDia1 N-terminus; they co-localize at the mitotic spindle; mDia1 knockdown by RNAi causes loss of PKD2 from mitotic spindles and alters intracellular Ca2+ release. Yeast two-hybrid screen, co-immunoprecipitation in native and transfected cells, RNAi knockdown, immunofluorescence, intracellular Ca2+ measurement The Journal of biological chemistry Medium 15123714
2005 Crystal structure of the dimeric mDia1 regulatory N-terminal domain reveals an intertwined six-helix bundle with two armadillo-repeat DIDs; NMR and biochemical mapping show that RhoA and DAD binding sites partially overlap on the DID, explaining how RhoA activates mDia1 by competing with DAD; RhoA binding also requires a flexibly tethered arm adjacent to the DID. X-ray crystallography, NMR spectroscopy, biochemical binding assays Molecular cell High 15866170
2006 Autoinhibition of mDia1 regulates not only in vitro actin assembly activity but also a novel membrane-localization activity in vivo; Rho-family GTPase binding relieves autoinhibition of both activities simultaneously, establishing dual regulation of localization and biochemical function as a general DRF principle. In vitro actin assembly assays, cellular localization of GFP-tagged wild-type vs. constitutively active and autoinhibited mDia1, GTPase binding-deficient mutants The Journal of cell biology Medium 16943183
2006 The Rho-mDia1 pathway regulates cell polarity and focal adhesion turnover during directed migration by aligning microtubules and actin filaments, enabling delivery of Apc/active Cdc42 to the cell front and c-Src to focal adhesions; mDia1 depletion by RNAi impairs both polarization and adhesion turnover. siRNA knockdown of mDia1 in rat C6 glioma cells, expression of active mDia1, live-cell imaging of Apc, Cdc42-FRET, c-Src localization by immunofluorescence Molecular and cellular biology High 16943426
2007 mDia1 is required for T lymphocyte chemotaxis and trafficking; mDia1-/- T cells show impaired actin filament formation, loss of polarity, reduced chemotaxis in vitro, and defective homing to secondary lymphoid organs in vivo despite normal integrin/chemokine receptor expression. mDia1 knockout mice, in vivo lymphocyte trafficking assay, in vitro chemotaxis, actin polymerization assay, flow cytometry The Journal of experimental medicine High 17682067
2007 Genetic disruption of Drf1 (mDia1) in mice causes age-dependent myeloproliferative defects including splenomegaly, hypercellular fibrotic bone marrow, and expansion of monocyte/macrophage and erythroid precursor populations, demonstrating an in vivo role for mDia1 in hematopoietic progenitor regulation. Homologous recombination knockout mouse, histopathology, flow cytometric cell surface marker analysis, bone marrow cell cycle analysis Cancer research High 17699759
2007 Galpha12/13-activated LARG associates with pericentrin and localizes to the MTOC and microtubule tracks; this Galpha12/13-LARG axis signals through RhoA to activate mDia1, which is required for MTOC polarization and microtubule dynamics in migrating fibroblasts. Galpha12/13-deficient mouse embryonic fibroblasts, co-immunoprecipitation of LARG and pericentrin, dominant-negative/constitutively active mDia1 and Galpha constructs, MTOC orientation assay, microtubule dynamics imaging Molecular biology of the cell Medium 17959834
2008 G-actin concentration directly regulates mDia1 actin nucleation frequency: elevated free G-actin (e.g., caused by low-dose latrunculin B) increases the actin nucleation rate of mDia1 via enhanced catalytic efficiency of the FH2 domain, independent of Rho signaling; this mechanism enables rapid actin polymer restoration at sites of actin disassembly. Single-molecule live-cell imaging of mDia1, unpolymerizable actin mutants, latrunculin B treatment, simulation analysis of G-actin concentration Journal of cell science High 18827014
2008 Memo is required for RhoA GTPase and its effector mDia1 to localize to the plasma membrane at the leading edge; loss of Memo impairs mDia1-dependent lamellipodial actin network organization, adhesion site formation, and microtubule outgrowth, placing Memo upstream of the RhoA-mDia1 axis in ErbB2-dependent cell migration. siRNA knockdown of Memo in breast carcinoma cells, immunofluorescence of RhoA/mDia1 localization, MT dynamics imaging, adhesion site quantification The Journal of cell biology Medium 18955552
2009 Loss of hDia1 (mDia1) in NK cells impairs microtubule cytoskeleton organization and targeting of microtubules to the lytic synapse but does not disrupt actin assembly at the synapse or cell adhesion, revealing a specific role for hDia1 in microtubule capture at the cell periphery during NK-mediated cytotoxicity. siRNA knockdown of hDia1 in NK cells, target cell lysis assay, immunofluorescence of actin and microtubules at the lytic synapse Current biology : CB Medium 19427913
2009 mDia1 forms an inducible complex with the Src kinase Hck and WASp in chemoattractant-stimulated neutrophils; mDia1 is required for chemokine-induced Hck membrane translocation, Hck activation, and Hck-mediated WASp tyrosine phosphorylation, establishing mDia1 as a scaffold linking Rho/actin to tyrosine kinase signaling at the leading edge. Co-immunoprecipitation, mDia1-/- neutrophils, immunofluorescence of Hck localization, Hck kinase activity assay, WASp phosphorylation analysis Biochemistry and cell biology Medium 19234535
2010 mDia1 targets v-Src (and by implication c-Src) from the perinuclear region to focal adhesions and the cell periphery via actin filament-dependent transport; in mDia1-deficient cells, v-Src fails to translocate to the membrane, leading to impaired tyrosine phosphorylation, suppressed podosome formation, reduced transformation, and decreased tumorigenesis/invasion in vivo. mDia1-knockout mouse embryonic fibroblasts, temperature-sensitive v-Src, immunofluorescence, focus formation, soft-agar colony formation, nude mouse tumor implantation Molecular and cellular biology High 20679479
2010 Flightless-I (Fli-I) directly binds mDia1 (and Daam1) and enhances their intrinsic actin assembly activity in vitro; Fli-I also promotes GTP-Rho-mediated relief of mDia1/Daam1 autoinhibition, identifying Fli-I as a positive cofactor for Rho-induced linear actin assembly. GST pulldown, co-immunoprecipitation, in vitro pyrene-actin polymerization assay, cell-based actin assembly assay The Journal of biological chemistry High 20223827
2010 Adenomatous polyposis coli (APC) C-terminal basic domain (APC-B) nucleates actin filaments and synergizes with mDia1; together, APC-B and mDia1 overcome the dual cellular barrier of profilin and capping protein to assemble actin, establishing APC as a mDia1 in vivo binding partner for cooperative actin nucleation. In vitro pyrene-actin nucleation assay with purified proteins, co-immunoprecipitation, EM of APC-B filaments, cell-based actin assembly assay The Journal of cell biology High 20566685
2010 mDia1 localizes to the mitotic spindle, and single-molecule fluorescence polarization demonstrates that mDia1 undergoes helical rotation along the long-pitch axis of the actin filament during processive elongation; this rotation oscillates with F-actin helix periodicity and is unaffected by actin-bound nucleotide or profilin. Single-molecule fluorescence polarization imaging, in vitro actin elongation from immobilized mDia1 Science (New York, N.Y.) High 21148346
2010 ACTH-stimulated cortisol biosynthesis requires RhoA and DIAPH1; ACTH/cAMP increases GTP-RhoA and promotes RhoA-DIAPH1 interaction; dominant-negative RhoA or DIAPH1 siRNA impairs mitochondrial trafficking (microtubule-dependent) and reduces cortisol biosynthesis while increasing androgen secretion, establishing a RhoA-DIAPH1 axis in steroidogenic organelle dynamics. Live-cell confocal video microscopy of mitochondria, RhoA activity assay, siRNA knockdown of DIAPH1, dominant-negative RhoA overexpression, steroid hormone measurement Endocrinology Medium 20591975
2010 The Rho-mDia1 pathway drives Golgi complex fragmentation into ministacks; constitutively active mDia1 alone is sufficient for Golgi dispersion; active mDia1 promotes formation of Rab6-positive transport vesicles and transiently localizes to these vesicles, revealing a role for mDia1 in Golgi membrane remodeling. Constitutively active and dominant-negative mDia1 expression, RhoA activation by LPA, cytoskeletal inhibitors (latrunculin B, blebbistatin, taxol), live imaging of Golgi markers, Rab6 vesicle analysis Molecular biology of the cell Medium 21680709
2011 The cytoplasmic domain of RAGE (ctRAGE) directly binds mDia1, and this interaction—mediated by an unusual α-turn in ctRAGE—is required for RAGE ligand-stimulated AKT phosphorylation and cell proliferation/migration, establishing mDia1 as the essential membrane-proximal intracellular effector of RAGE signaling. NMR structure determination of ctRAGE, NMR mapping of ctRAGE-mDia1 interaction interface, mutagenesis of the α-turn, AKT phosphorylation and cell migration assays The Journal of biological chemistry High 22194616
2011 INF2, mDia1, and mDia2 FH1FH2C constructs all bind microtubules with high affinity (Kd < 100 nM); mDia1 shows saturating binding at ~1:3 stoichiometry (dimer:tubulin dimer) but does not bundle microtubules; microtubules moderately inhibit actin polymerization by mDia1; actin monomers do not affect mDia1 microtubule binding, demonstrating simultaneous actin and microtubule engagement. In vitro microtubule co-sedimentation assay, microtubule catastrophe rate measurement, actin polymerization assay with purified proteins Molecular biology of the cell High 21998204
2011 CLIP-170 directly interacts with the FH2 domain of mDia1 and controls mDia1 recruitment to the phagocytic cup during complement receptor (alphaMbeta2/CR3)-mediated phagocytosis in macrophages; CLIP-170 knockdown reduces mDia1 recruitment and actin polymerization at the phagocytic cup. RNAi knockdown, dominant-negative CLIP-170, direct binding assay (CLIP-170-FH2 interaction), live-cell imaging of phagocytosis, immunofluorescence The Journal of cell biology Medium 19114595
2011 mDia1 and WAVE2 directly interact with IRSp53 within filopodia (shown by FRET); mDia1 and WAVE2 synergize with IRSp53 to form filopodia; knockdown of mDia1 or WAVE2 decreases IRSp53-induced filopodium formation, establishing mDia1 as a specific SH3-domain partner of IRSp53 in filopodium biogenesis. Acceptor photobleaching FRET, siRNA knockdown, time-lapse imaging, co-immunoprecipitation The Journal of biological chemistry Medium 22179776
2011 Rif GTPase directly interacts with mDia1 (but not mDia2) within filopodia to drive filopodium formation independently of Cdc42 effectors (N-WASP, IRSp53) and Rac effectors (WAVE1, WAVE2); dominant-negative mDia1 or mDia1 siRNA reduces Rif-induced filopodia. FRET in filopodia, siRNA knockdown, dominant-negative mDia1, time-lapse imaging The Journal of biological chemistry Medium 21339294
2012 Actin-capping protein is a physiological regulator of mDia1 that promotes stable detyrosinated microtubule formation; by blocking mDia1 translocation on actin filament barbed ends, capping protein releases mDia1 to act on microtubules; knockdown of capping protein reduces stable MT levels in an mDia1-dependent manner. siRNA knockdown of mDia1 and capping protein, latrunculin A and jasplakinolide treatment, immunofluorescence of stable (Glu) MTs, mDia1 barbed-end translocation assay Molecular biology of the cell Medium 22918941
2012 mDia1 controls caveolin-1 (Cav1)/caveolae domain organization downstream of Abl kinases; mDia1 knockdown causes Cav1/caveolae clustering and defective inward trafficking upon loss of cell adhesion; constitutively active mDia1 rescues the Cav1 pool and inward trafficking in Abl-deficient cells. mDia1 siRNA knockdown, constitutively active mDia1 expression, Abl-deficient cells, live imaging of Cav1, electron microscopy of caveolae Journal of cell science Medium 22454521
2012 mDia1 is required for RAGE ligand (AGE)-induced membrane translocation of c-Src, which leads to Rac1 activation, redox phosphorylation of AKT/GSK3β, and vascular smooth muscle cell migration; mDia1 is upregulated in the neointima after vascular injury and its loss significantly reduces pathological neointimal expansion. In vivo femoral artery denudation injury in mDia1 KO and WT mice, primary murine aortic SMC culture, mDia1 siRNA, immunofluorescence of c-Src, Rac1-GTP pull-down, AKT/GSK3β phosphorylation Circulation research High 22511750
2010 Crystal structure of the mDia1 N-terminal regulatory domain in complex with a C-terminal FH2+DAD fragment reveals a tetrameric assembly of two interlocked N+C dimers; the structure shows that DAD engagement by the N-terminus is incompatible with actin filament formation on the FH2 domain, providing structural models for autoinhibition. X-ray crystallography, size exclusion chromatography, in-solution biochemical analysis of oligomeric state PloS one High 20927338
2014 DIAPH1 (mDia1) negatively regulates megakaryocyte proplatelet formation (PPF) by controlling actin and microtubule dynamics; inhibition of both DIAPH1 and ROCK/myosin II together increases PPF, revealing coordinate regulation of both cytoskeletons by these two RhoA effectors. mDia1-knockout mouse megakaryocytes, DIAPH1 siRNA, ROCK inhibitor, confocal imaging of proplatelet formation, cytoskeletal markers Blood High 25298036
2015 mDia1 initiates lamellipodia and ruffles by nucleating linear actin filaments that serve as seeds for Arp2/3 complex-dependent branched network formation; mDia1 is an EGF-regulated actin nucleator that localizes within nascent and mature membrane ruffles and cooperates sequentially with Arp2/3. mDia1 knockdown and rescue experiments, optogenetics, Arp2/3 pharmacological inhibition (CK-666), fluorescence imaging of ruffles and lamellipodia, migration assay Journal of cell science High 26349808
2016 A gain-of-function DIAPH1 R1213* variant truncates the DAD domain, disrupts DID-DAD autoinhibitory interaction, and causes constitutive DIAPH1 activation, leading to increased filamentous actin, stable microtubules in platelets and megakaryocytes, reduced proplatelet formation, macrothrombocytopenia, and sensorineural hearing loss. Patient-derived cell studies, DIAPH1 R1213* overexpression in cells, immunofluorescence of F-actin and microtubules, flow cytometry, in vitro megakaryocyte culture Blood High 26912466
2016 An mDia1-INF2 formin activation cascade, scaffolded by IQGAP1, regulates stable detyrosinated microtubule formation downstream of LPA/RhoA; mDia1 promotes INF2 localization to microtubules, and the N-terminus of IQGAP1 directly binds the C-terminus of INF2 to facilitate a tripartite complex. siRNA knockdown of mDia1, INF2, and IQGAP1; constitutively active formin mutants; direct binding assay (IQGAP1-INF2); immunofluorescence of Glu-MTs; LPA stimulation Molecular biology of the cell Medium 27030671
2016 DIAPH1 c.3634+1G>T and c.3610C>T mutations cause C-terminal truncation of DIA1 that disrupts the autoinhibitory DID-DAD interaction (specifically a basic RRKR motif in the DAD), constitutively activating DIA1; this causes increased rates of directional actin polymerization, elongated microvilli, progressive hair cell loss, and DFNA1 hearing loss in mice. Patient-derived mutation analysis, in vitro DID-DAD binding assay, single-molecule actin polymerization imaging, FLAG-DIA1(R1204X) knock-in mouse, auditory brainstem response, hair cell morphology EMBO molecular medicine High 27707755
2016 Small molecule screening identified 13 competitive inhibitors of the ctRAGE-DIAPH1 interaction; these compounds inhibit RAGE-dependent molecular processes in vitro and in vivo, confirming that the ctRAGE-DIAPH1 protein-protein interaction is pharmacologically tractable and functionally important for RAGE signaling. Small molecule screen (58,000 compounds), competitive binding assay for ctRAGE-DIAPH1 interaction, in vitro and in vivo RAGE signaling assays Scientific reports Medium 26936329
2018 Helical rotation of mDia1 during processive actin elongation converts F-actin into a cofilin-resistant state both in vitro and in vivo; tethering mDia1 and the pointed end simultaneously causes untwisting of the F-actin long-pitch helix, which inhibits cofilin binding and severing; constitutively active mDia1ΔC63 in cells produces long-lived, cofilin-dissociating F-actin. Electron micrography of actin helix twist, in vitro cofilin binding and severing assay with tethered vs. free mDia1, single-molecule imaging of mDia1ΔC63 in cells, F-actin lifetime measurement Proceedings of the National Academy of Sciences of the United States of America High 29760064
2018 Cdk1 phosphorylates DIAPH1 during mitosis to prevent profilin1 binding, thereby maintaining cortical tension at a constant level in metaphase; loss of DIAPH1 phosphorylation causes excess cortical F-actin accumulation, increased cortical tension, and delayed anaphase onset due to spindle assembly checkpoint (SAC) activation. Cdk1 kinase assay, phospho-site mutant DIAPH1 expression, cortical tension measurement (AFM/osmotic assay), SAC reporter, profilin1 binding assay, intra-kinetochore stretch measurement Nature communications High 30816115
2018 Diaph1 (mDia1) promotes myofibroblastic activation of hepatic stellate cells by binding to both TGFβ receptor II (TβRII) and Rab5a via its N-terminal domain; Diaph1 stimulates Rab5a GTPase activity, increases TβRII endocytosis, and is required for SMAD3 phosphorylation and TGFβ1-induced fibrogenic gene expression. shRNA knockdown of Diaph1, SMIFH2 formin inhibitor, co-immunoprecipitation of Diaph1-TβRII and Diaph1-Rab5a, Rab5a activity assay, TβRII internalization assay, SMAD3 phosphorylation, tumor implantation mouse model FASEB journal High 32304339
2018 mDia1 and mDia3 together generate a dynamic cortical F-actin meshwork in Sertoli cells that is continuous with contractile actomyosin bundles; double KO of mDia1/3 impairs this architecture, induces ectopic espin1-containing bundles, disrupts Sertoli-germ cell interactions, and causes spermatogenic failure, establishing mDia1/3 as essential for male fertility. mDia1 and mDia3 double-knockout mice, superresolution microscopy, single-molecule imaging of actin dynamics, immunofluorescence, spermatogenesis histology PLoS biology High 30256801
2019 mDia1 activity is required for DIAPH1-mediated regulation of SRF-target genes, sarcoplasmic reticulum Ca2+ ATPase expression, and sodium-calcium exchanger expression in cardiomyocytes; Diaph1 knockout reduces infarct size and improves contractile function after ischemia-reperfusion in mice. Diaph1-/- mouse I/R model, siRNA knockdown in H9C2 cells, actin polymerization assay, SRF-reporter, SERCA and NCX western blot EBioMedicine Medium 29239839
2020 SPIN90 forms a ternary complex with Arp2/3 and mDia1 in vitro; this complex greatly enhances actin filament nucleation, producing unbranched filaments with mDia1 at barbed ends and SPIN90-Arp2/3 at pointed ends; SPIN90 efficiently recruits mDia1 to SPIN90-Arp2/3-nucleated filaments, lowering branching density and increasing long mDia1-elongated filaments in the cortex. In vitro actin assembly reconstitution, TIRF microscopy of single filaments, biochemical pulldown of ternary complex, cell cortex imaging Nature cell biology High 32572169
2020 Formin-mediated actin polymerization (specifically by mDia1 and mDia3 at the immune synapse) is required for spatiotemporal control of Zap70-LAT phosphorylation during T cell receptor activation; formin inhibition blocks LAT phosphorylation without affecting Zap70 activation; mDia1/mDia3 localize to the IS upon TCR stimulation and their genetic absence impairs this pathway. mDia1 and mDia3 knockout mice, formin inhibitor (SMIFH2), LAT and Zap70 phosphorylation assay, high-resolution immunofluorescence and 3D reconstruction of IS Science advances High 31911947
2021 mDia1-mediated actin polymerization at focal adhesions is activated by contractile force in a pulsatile manner; suppression of mDia1 actin polymerization increases tension on stress fibers and elevates spontaneous stress fiber damage, while reducing efficiency of zyxin-mediated stress fiber repair, establishing force-dependent mDia1 activity as a safety valve against mechanical cytoskeletal damage. Live-cell imaging of mDia1 activity (mDia1-FRET biosensor or GFP-mDia1), mathematical modeling, laser ablation of stress fibers, zyxin-mCherry repair assay, traction force microscopy Developmental cell High 34822787
2021 RAGE229, a small-molecule antagonist of ctRAGE-DIAPH1 interaction, binds ctRAGE (defined by solution NMR), suppresses RAGE-DIAPH1 binding and FRET, and attenuates diabetic complications in mice including reduced mesangial sclerosis, inflammation, and kidney dysfunction, without lowering blood glucose. NMR spectroscopy, FRET assay of ctRAGE-DIAPH1 binding, in vivo streptozotocin diabetes mouse model, kidney histopathology, plasma cytokine measurement Science translational medicine High 34818060
2023 DIAPH1 mediates SREBP1 nuclear translocation (independently of carbohydrate/insulin cues) through the actin cytoskeleton, promoting hepatic lipid synthesis genes (Acaca, Acacb, Gpat2, Fasn); Diaph1 deletion reduces atherosclerosis and plasma cholesterol/triglycerides in Ldlr-/- mice on Western diet. Ldlr-/- × Diaph1-/- mouse atherosclerosis model, hepatic gene expression (qPCR), SREBP1 nuclear translocation immunofluorescence, plasma lipid measurement, actin cytoskeleton manipulation Communications biology Medium 36932214

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. The Journal of cell biology 1060 11402062
1999 Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nature cell biology 731 10559899
2009 Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion. Cancer metastasis reviews 437 19160018
2003 The mouse Formin mDia1 is a potent actin nucleation factor regulated by autoinhibition. Current biology : CB 356 12906795
1997 Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous. Science (New York, N.Y.) 318 9360932
2001 Coordination of microtubules and the actin cytoskeleton by the Rho effector mDia1. Nature cell biology 273 11146620
2003 A conserved mechanism for Bni1- and mDia1-induced actin assembly and dual regulation of Bni1 by Bud6 and profilin. Molecular biology of the cell 236 14657240
2005 Structural basis of Rho GTPase-mediated activation of the formin mDia1. Molecular cell 209 15866170
2003 Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42. Current biology : CB 205 12676083
2002 ROCK and mDia1 antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts. The Journal of cell biology 181 12021256
2002 The diaphanous-related formin mDia1 controls serum response factor activity through its effects on actin polymerization. Molecular biology of the cell 160 12429848
2006 The Rho-mDia1 pathway regulates cell polarity and focal adhesion turnover in migrating cells through mobilizing Apc and c-Src. Molecular and cellular biology 153 16943426
2022 WTAP-mediated m6A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis. Cell death and differentiation 142 34999731
2010 Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1. The Journal of cell biology 137 20566685
2016 A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss. Blood 122 26912466
2011 Differential interactions of the formins INF2, mDia1, and mDia2 with microtubules. Molecular biology of the cell 114 21998204
2006 Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLalpha and mDia1. The Journal of cell biology 114 16943183
2007 Impaired T lymphocyte trafficking in mice deficient in an actin-nucleating protein, mDia1. The Journal of experimental medicine 111 17682067
2001 Localization of a mammalian homolog of diaphanous, mDia1, to the mitotic spindle in HeLa cells. Journal of cell science 108 11171383
2011 Signal transduction in receptor for advanced glycation end products (RAGE): solution structure of C-terminal rage (ctRAGE) and its binding to mDia1. The Journal of biological chemistry 107 22194616
2007 T cell responses in mammalian diaphanous-related formin mDia1 knock-out mice. The Journal of biological chemistry 104 17595162
2016 Small Molecule Inhibition of Ligand-Stimulated RAGE-DIAPH1 Signal Transduction. Scientific reports 99 26936329
2008 Memo-RhoA-mDia1 signaling controls microtubules, the actin network, and adhesion site formation in migrating cells. The Journal of cell biology 97 18955552
2010 Rotational movement of the formin mDia1 along the double helical strand of an actin filament. Science (New York, N.Y.) 94 21148346
2008 The microtubule-binding protein CLIP-170 coordinates mDia1 and actin reorganization during CR3-mediated phagocytosis. The Journal of cell biology 88 19114595
2004 PKD2 interacts and co-localizes with mDia1 to mitotic spindles of dividing cells: role of mDia1 IN PKD2 localization to mitotic spindles. The Journal of biological chemistry 87 15123714
2012 Formin mDia1 mediates vascular remodeling via integration of oxidative and signal transduction pathways. Circulation research 84 22511750
2011 mDia1 and WAVE2 proteins interact directly with IRSp53 in filopodia and are involved in filopodium formation. The Journal of biological chemistry 77 22179776
2007 Myeloproliferative defects following targeting of the Drf1 gene encoding the mammalian diaphanous related formin mDia1. Cancer research 71 17699759
2015 Initiation of lamellipodia and ruffles involves cooperation between mDia1 and the Arp2/3 complex. Journal of cell science 70 26349808
2011 Involvement of the Rho-mDia1 pathway in the regulation of Golgi complex architecture and dynamics. Molecular biology of the cell 68 21680709
2014 Homozygous loss of DIAPH1 is a novel cause of microcephaly in humans. European journal of human genetics : EJHG 65 24781755
2014 The formin DIAPH1 (mDia1) regulates megakaryocyte proplatelet formation by remodeling the actin and microtubule cytoskeletons. Blood 64 25298036
2021 Small-molecule antagonism of the interaction of the RAGE cytoplasmic domain with DIAPH1 reduces diabetic complications in mice. Science translational medicine 63 34818060
2016 Constitutive activation of DIA1 (DIAPH1) via C-terminal truncation causes human sensorineural hearing loss. EMBO molecular medicine 61 27707755
2012 Actin-capping protein promotes microtubule stability by antagonizing the actin activity of mDia1. Molecular biology of the cell 60 22918941
2019 The Receptor for Advanced Glycation End Products (RAGE) and DIAPH1: Implications for vascular and neuroinflammatory dysfunction in disorders of the central nervous system. Neurochemistry international 54 30902646
2012 Caveolar domain organization and trafficking is regulated by Abl kinases and mDia1. Journal of cell science 53 22454521
2011 Role of RhoA and its effectors ROCK and mDia1 in the modulation of deformation-induced FAK, ERK, p38, and MLC motogenic signals in human Caco-2 intestinal epithelial cells. American journal of physiology. Cell physiology 50 21849669
2016 An mDia1-INF2 formin activation cascade facilitated by IQGAP1 regulates stable microtubules in migrating cells. Molecular biology of the cell 49 27030671
2021 DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease. JAMA neurology 48 34125151
2010 Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells. Blood 47 20881208
2009 Distinct roles for the actin nucleators Arp2/3 and hDia1 during NK-mediated cytotoxicity. Current biology : CB 47 19913427
2021 Loss of DIAPH1 causes SCBMS, combined immunodeficiency, and mitochondrial dysfunction. The Journal of allergy and clinical immunology 46 33662367
2020 SPIN90 associates with mDia1 and the Arp2/3 complex to regulate cortical actin organization. Nature cell biology 46 32572169
2016 Extension of the clinical and molecular phenotype of DIAPH1-associated autosomal dominant hearing loss (DFNA1). Clinical genetics 46 27808407
2008 G-actin regulates rapid induction of actin nucleation by mDia1 to restore cellular actin polymers. Journal of cell science 46 18827014
2013 The formins FMNL1 and mDia1 regulate coiling phagocytosis of Borrelia burgdorferi by primary human macrophages. Infection and immunity 45 23460512
2007 LARG and mDia1 link Galpha12/13 to cell polarity and microtubule dynamics. Molecular biology of the cell 45 17959834
2015 Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures. American journal of medical genetics. Part A 44 26463574
2014 Aberrant overexpression of CD14 on granulocytes sensitizes the innate immune response in mDia1 heterozygous del(5q) MDS. Blood 44 24891322
2001 Characterization of functional domains of mDia1, a link between the small GTPase Rho and the actin cytoskeleton. Journal of cell science 43 11707518
2010 Crystal structure of a complex between amino and carboxy terminal fragments of mDia1: insights into autoinhibition of diaphanous-related formins. PloS one 42 20927338
2018 Helical rotation of the diaphanous-related formin mDia1 generates actin filaments resistant to cofilin. Proceedings of the National Academy of Sciences of the United States of America 37 29760064
2017 The Formin, DIAPH1, is a Key Modulator of Myocardial Ischemia/Reperfusion Injury. EBioMedicine 36 29239839
2011 Rif-mDia1 interaction is involved in filopodium formation independent of Cdc42 and Rac effectors. The Journal of biological chemistry 36 21339294
2010 Flightless-I (Fli-I) regulates the actin assembly activity of diaphanous-related formins (DRFs) Daam1 and mDia1 in cooperation with active Rho GTPase. The Journal of biological chemistry 36 20223827
2016 HYDROGEN-RICH MEDIUM AMELIORATES LIPOPOLYSACCHARIDE-INDUCED BARRIER DYSFUNCTION VIA RHOA-MDIA1 SIGNALING IN CACO-2 CELLS. Shock (Augusta, Ga.) 34 26529665
1998 Further characterization of the DFNA1 audiovestibular phenotype. Archives of otolaryngology--head & neck surgery 33 9639482
2020 FPS-ZM1 Alleviates Neuroinflammation in Focal Cerebral Ischemia Rats via Blocking Ligand/RAGE/DIAPH1 Pathway. ACS chemical neuroscience 32 33300334
2010 RhoA and DIAPH1 mediate adrenocorticotropin-stimulated cortisol biosynthesis by regulating mitochondrial trafficking. Endocrinology 31 20591975
2018 Phenotype description and response to thrombopoietin receptor agonist in DIAPH1-related disorder. Blood advances 30 30232087
2007 Up-regulation of myometrial RHO effector proteins (PKN1 and DIAPH1) and CPI-17 (PPP1R14A) phosphorylation in human pregnancy is associated with increased GTP-RHOA in spontaneous preterm labor. Biology of reproduction 30 17301291
2013 Expression of DIAPH1 is up-regulated in colorectal cancer and its down-regulation strongly reduces the metastatic capacity of colon carcinoma cells. International journal of cancer 29 24105619
2021 Force-dependent activation of actin elongation factor mDia1 protects the cytoskeleton from mechanical damage and promotes stress fiber repair. Developmental cell 26 34822787
2018 Mdia1 is Crucial for Advanced Glycation End Product-Induced Endothelial Hyperpermeability. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 29490301
2018 IP3R3 silencing induced actin cytoskeletal reorganization through ARHGAP18/RhoA/mDia1/FAK pathway in breast cancer cell lines. Biochimica et biophysica acta. Molecular cell research 26 29630900
2016 Glycation & the RAGE axis: targeting signal transduction through DIAPH1. Expert review of proteomics 26 27967251
2021 AGE/RAGE/DIAPH1 axis is associated with immunometabolic markers and risk of insulin resistance in subcutaneous but not omental adipose tissue in human obesity. International journal of obesity (2005) 25 34103691
2014 Formin mDia1, a downstream molecule of FMNL1, regulates Profilin1 for actin assembly and spindle organization during mouse oocyte meiosis. Biochimica et biophysica acta 25 25447542
2006 HAN11 binds mDia1 and controls GLI1 transcriptional activity. Journal of dermatological science 25 16887337
2019 DIAPH1 Is Upregulated and Inhibits Cell Apoptosis through ATR/p53/Caspase-3 Signaling Pathway in Laryngeal Squamous Cell Carcinoma. Disease markers 24 30733838
2018 Deletion of the formin Diaph1 protects from structural and functional abnormalities in the murine diabetic kidney. American journal of physiology. Renal physiology 24 30132346
2018 BIG2-ARF1-RhoA-mDia1 Signaling Regulates Dendritic Golgi Polarization in Hippocampal Neurons. Molecular neurobiology 23 29455446
2017 Progressive macrothrombocytopenia and hearing loss in a large family with DIAPH1 related disease. American journal of medical genetics. Part A 22 28815995
2017 Knockdown of Diaph1 expression inhibits migration and decreases the expression of MMP2 and MMP9 in human glioma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 29035824
2018 Enteropathogenic E. coli relies on collaboration between the formin mDia1 and the Arp2/3 complex for actin pedestal biogenesis and maintenance. PLoS pathogens 21 30550556
2010 mDia1 targets v-Src to the cell periphery and facilitates cell transformation, tumorigenesis, and invasion. Molecular and cellular biology 21 20679479
2019 Mammalian diaphanous-related formin 1 (mDia1) coordinates mast cell migration and secretion through its actin-nucleating activity. The Journal of allergy and clinical immunology 20 31279009
2023 DIAPH1 mediates progression of atherosclerosis and regulates hepatic lipid metabolism in mice. Communications biology 19 36932214
2022 The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications. International journal of molecular sciences 19 35562970
2018 Diaphanous 1 (DIAPH1) is Highly Expressed in the Aged Human Medial Temporal Cortex and Upregulated in Myeloid Cells During Alzheimer's Disease. Journal of Alzheimer's disease : JAD 19 29966194
2018 mDia1/3 generate cortical F-actin meshwork in Sertoli cells that is continuous with contractile F-actin bundles and indispensable for spermatogenesis and male fertility. PLoS biology 19 30256801
2018 mDia1 and Cdc42 Regulate Activin B-Induced Migration of Bone Marrow-Derived Mesenchymal Stromal Cells. Stem cells (Dayton, Ohio) 19 30358011
2020 Association of DIAPH1 gene polymorphisms with ischemic stroke. Aging 18 31899686
2020 mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse. Science advances 18 31911947
2020 A novel variant in diaphanous homolog 1 (DIAPH1) as the cause of auditory neuropathy in a Chinese family. International journal of pediatric otorhinolaryngology 18 32087478
2020 CREB1-induced lncRNA LEF1-AS1 contributes to colorectal cancer progression via the miR-489/DIAPH1 axis. Biochemical and biophysical research communications 18 32248974
2020 Protein diaphanous homolog 1 (Diaph1) promotes myofibroblastic activation of hepatic stellate cells by regulating Rab5a activity and TGFβ receptor endocytosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 32304339
2012 mDia1-3 in mammalian filopodia. Communicative & integrative biology 18 23060957
2009 Src kinase Hck association with the WASp and mDia1 cytoskeletal regulators promotes chemoattractant-induced Hck membrane targeting and activation in neutrophils. Biochemistry and cell biology = Biochimie et biologie cellulaire 18 19234535
2009 Loss of RhoB expression enhances the myelodysplastic phenotype of mammalian diaphanous-related Formin mDia1 knockout mice. PloS one 18 19768111
2022 Formin protein DIAPH1 positively regulates PD-L1 expression and predicts the therapeutic response to anti-PD-1/PD-L1 immunotherapy. Clinical immunology (Orlando, Fla.) 17 36503156
2021 The cross-talk between RAGE and DIAPH1 in neurological complications of diabetes: A review. The European journal of neuroscience 17 34449932
2019 RHOA and mDia1 Promotes Apoptosis of Breast Cancer Cells Via a High Dose of Doxorubicin Treatment. Open life sciences 17 33817200
2015 Drosophila homologue of Diaphanous 1 (DIAPH1) controls the metastatic potential of colon cancer cells by regulating microtubule-dependent adhesion. Oncotarget 17 26124177
2019 Cdk1-mediated DIAPH1 phosphorylation maintains metaphase cortical tension and inactivates the spindle assembly checkpoint at anaphase. Nature communications 16 30816115
2015 Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK. PloS one 16 26674774
2016 A novel missense variant in the DIAPH1 gene in a Korean family with autosomal dominant nonsyndromic hearing loss. Genes & genetic systems 15 28003573
2009 RhoA effector mDia1 is required for PI 3-kinase-dependent actin remodeling and spreading by thrombin in platelets. Biochemical and biophysical research communications 15 19470376

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