| 1997 |
DIAPH1 (human diaphanous homolog) was identified as a profilin ligand and target of Rho GTPase that regulates polymerization of actin; a protein-truncating splice-donor mutation causes autosomal dominant sensorineural hearing loss DFNA1. |
Genetic linkage mapping + mutation identification in a large kindred; functional annotation as profilin ligand and Rho target |
Science |
High |
9360932
|
| 1999 |
GTP-bound RhoA activates mDia1 by disrupting its intramolecular autoinhibitory interaction; active mDia1 induces formation of thin actin stress fibers and cooperates with ROCK to produce mature stress fibers. |
Constitutively active and dominant-negative mutant expression in cells; co-expression with ROCK inhibitors; fluorescence microscopy of actin structures |
Nature cell biology |
High |
10559899
|
| 2001 |
mDia1 mediates force-induced focal contact formation downstream of Rho, independently of ROCK-mediated myosin II contractility; integrin-containing focal complexes act as mechanosensors that respond to externally applied tension via mDia1. |
Micropipette force application to cells; C3 transferase Rho inhibition; constitutively active mDia1 rescue; GFP-vinculin/paxillin live imaging; ROCK and myosin II inhibitors |
The Journal of cell biology |
High |
11402062
|
| 2001 |
Active mDia1 (via its FH1 and FH2 regions) coordinates microtubule alignment parallel to F-actin bundles; the FH2 region is required for microtubule alignment and cell elongation, whereas FH1 mediates actin effects. |
Expression of mDia1 deletion and point mutants (FH1/FH2) in HeLa cells; immunofluorescence of microtubules and F-actin |
Nature cell biology |
High |
11146620
|
| 2001 |
mDia1 localizes to the mitotic spindle from prophase to telophase in HeLa cells; spindle localization is determined by a 173-amino-acid sequence in the FH3 region (Leu434 and Leu455 required) and is independent of Rho activity. |
Immunocytochemistry with anti-mDia1 antibody using instantaneous fixation; GFP-mDia1 truncation mutants; mitotic spindle fractionation + Western blot; microinjection of C3/Val14RhoA |
Journal of cell science |
High |
11171383
|
| 2001 |
The FH1 domain of mDia1 binds profilin in vitro and in cells; the RBD (Rho-binding domain) complexes with the C-terminal CIID autoinhibitory module; overexpression of the RBD alone causes spontaneous ruffling, loss of stress fibers, and upregulation of Rac activity. |
In vitro binding assays; transfection of deletion constructs; dominant-negative Rac co-expression; fluorescence microscopy |
Journal of cell science |
Medium |
11707518
|
| 2002 |
mDia1 mediates Rho-dependent Rac activation through a Cas phosphorylation/Crk-II/DOCK180 pathway that is antagonized by ROCK; active mDia1 dominant-negative inhibits membrane ruffle formation induced by ROCK inhibition. |
ROCK inhibitor (Y-27632) vs. C3 exoenzyme comparison; dominant-negative mDia1; Rac-GTP pull-down assay; phosphotyrosine analysis; dominant-negative Cas/Crk mutants |
The Journal of cell biology |
High |
12021256
|
| 2002 |
mDia1 activates serum response factor (SRF) through actin polymerization; the FH2 domain (and extended C-terminal region) is required for both F-actin assembly and SRF activation; actin depletion of the G-actin pool downstream of mDia1 is the signal to SRF. |
SRF luciferase reporter assay; mDia1 deletion/point mutants; nonpolymerizable actin mutant; dominant-negative mDia1 derivatives blocking serum/LPA-induced SRF |
Molecular biology of the cell |
High |
12429848
|
| 2003 |
Mouse mDia1 FH2-containing constructs are potent actin nucleators in vitro; the FH1 domain is required for nucleation from profilin-bound actin monomers; the N-terminal GBD strongly inhibits C-terminal actin nucleation activity (autoinhibition model); RhoA partially relieves this inhibition. |
In vitro pyrene-actin polymerization assay; recombinant mDia1 domain constructs; profilin-actin nucleation assay; gel filtration (multimer analysis) |
Current biology |
High |
12906795
|
| 2003 |
mDia1 FH2 dimers nucleate and processively associate with actin filament barbed ends, protecting them from capping protein; this mechanism is conserved between yeast Bni1 and mammalian mDia1. |
In vitro pyrene-actin polymerization; TIRF microscopy; capping protein competition assay; in vivo complementation of bni1 mutant yeast with mDia1 |
Molecular biology of the cell |
High |
14657240
|
| 2003 |
Genetic disruption of Drf1 (mDia1) reveals that mDia1 loss leads to compensatory upregulation of Drf3 (mDia2), which acts as a Cdc42 effector via a CRIB-like motif in its GBD; Drf3 is recruited by Cdc42 to the leading edge and MTOC during migration. |
Embryonic stem cell-derived Drf1 knockout cell lines; dominant-negative Drf3 and anti-Drf3 antibody microinjection; FRET analysis of Cdc42-Drf3 binding; fluorescence microscopy |
Current biology |
Medium |
12676083
|
| 2004 |
mDia1 interacts with PKD2 (polycystin-2) at the mitotic spindle; the interaction is mediated by the PKD2 cytoplasmic C-terminus binding to the mDia1 N-terminus; mDia1 knockdown displaces PKD2 from mitotic spindles and alters intracellular Ca2+ release. |
Yeast two-hybrid screen; co-immunoprecipitation in native and transfected cells; RNAi knockdown; immunofluorescence co-localization; Ca2+ measurements |
The Journal of biological chemistry |
High |
15123714
|
| 2005 |
Crystal structure of the dimeric mDia1 regulatory N-terminal domain reveals an intertwined six-helix bundle with two DID modules (five armadillo repeats each); NMR and biochemical mapping show RhoA and DAD binding sites partially overlap on the DID, explaining GTPase-mediated autoinhibition relief. |
X-ray crystallography; NMR chemical-shift mapping; biochemical binding assays (pulldown/ITC) |
Molecular cell |
High |
15866170
|
| 2006 |
mDia1 autoinhibition (DID-DAD intramolecular interaction) controls both in vitro actin assembly activity and in vivo membrane localization; Cdc42 relieves FRLα autoinhibition, demonstrating that this is a general DRF regulatory principle. |
In vitro actin assembly assay; live-cell membrane localization imaging; phagocytosis assay; dominant-negative and constitutively active DRF mutants |
The Journal of cell biology |
High |
16943183
|
| 2006 |
The Rho-mDia1 pathway regulates directed cell migration by aligning microtubules (delivering APC and active Cdc42 to the cell front for polarity) and actin filaments (recruiting active c-Src to focal adhesions for adhesion turnover). |
RNAi knockdown of mDia1 in C6 glioma cells; constitutively active mDia1 expression; live fluorescence imaging of APC, Cdc42, c-Src localization; wound healing/migration assays |
Molecular and cellular biology |
High |
16943426
|
| 2006 |
HAN11 binds the FH2 actin-binding domain of mDia1; overexpression of mDia1 or active RhoA causes translocation of HAN11 from nucleus to cytoplasm; mDia1 and HAN11 together repress DYRK1A-dependent GLI1 transcriptional activity. |
TAP-tag purification; GST pull-down; luciferase transcription assay; immunofluorescence microscopy |
Journal of dermatological science |
Medium |
16887337
|
| 2007 |
mDia1 knockout mice develop lymphopenia with T cells showing impaired chemotaxis, reduced actin filament formation, impaired polarity in response to chemotactic stimuli, and poor adhesion to extracellular matrix; ERK1/2 activation is diminished in activated Drf1-/- T cells. |
Drf1 gene knockout mice; in vitro chemotaxis assays; actin staining; cell adhesion assays; flow cytometry; ERK phosphorylation western blot |
The Journal of experimental medicine |
High |
17682067
|
| 2007 |
mDia1 loss (Drf1-/- mice) causes age-dependent myeloproliferative defects including splenomegaly, fibrotic hypercellular bone marrow, extramedullary hematopoiesis, and expansion of myeloid progenitors, resembling human myeloproliferative/myelodysplastic syndrome. |
Homologous recombination knockout mice; hematopoietic phenotyping; flow cytometry of surface markers; histology |
Cancer research |
High |
17699759
|
| 2007 |
LARG (RhoGEF) and mDia1 link Gα12/13 signaling to MTOC polarity and microtubule dynamics during directed cell migration; LARG localizes to the MTOC via pericentrin and along microtubule tracks. |
Gα12/13-deficient mouse embryonic fibroblasts; LARG knockdown; dominant-negative mDia1; MTOC polarity assay; immunofluorescence |
Molecular biology of the cell |
Medium |
17959834
|
| 2008 |
Memo acts upstream of RhoA-mDia1 to localize RhoA and mDia1 to the plasma membrane at the leading edge, coordinating lamellipodial actin network organization, adhesion site formation, and microtubule outgrowth during ErbB2-driven cell migration. |
Memo siRNA knockdown; immunofluorescence of RhoA/mDia1 localization; adhesion site live imaging; MT dynamics analysis |
The Journal of cell biology |
Medium |
18955552
|
| 2008 |
G-actin accumulation acts as a physiological cue to enhance mDia1-catalyzed actin nucleation frequency via increased catalytic efficiency of its FH2 domain; this rapid restoration mechanism is distinct from Arp2/3 regulation. |
Single-molecule live-cell imaging of mDia1 in cells; latrunculin B and unpolymerizable actin mutant treatments; FH2-domain-only constructs; computational simulation of G-actin dynamics |
Journal of cell science |
High |
18827014
|
| 2008 |
CLIP-170 directly interacts with the mDia1 FH2 domain, recruits mDia1 to the phagocytic cup during CR3-mediated phagocytosis, and thereby controls actin polymerization required for phagocytosis; this interaction is negatively regulated during phagocytosis. |
RNAi knockdown; dominant-negative approaches; co-immunoprecipitation; live imaging of CLIP-170 and mDia1 at phagocytic cup; phagocytosis efficiency assay |
The Journal of cell biology |
High |
19114595
|
| 2009 |
mDia1 in NK cells mediates microtubule targeting to the lytic synapse (but not actin assembly there), enabling target cell lysis; loss of hDia1 perturbs the microtubule cytoskeleton without disrupting actin assembly at the lytic synapse. |
siRNA knockdown of Arp2/3 or hDia1 in NK cells; cytotoxicity assay; immunofluorescence of actin and microtubules at lytic synapse |
Current biology |
Medium |
19913427
|
| 2009 |
Hck kinase forms a complex with mDia1 and WASp in chemoattractant-stimulated neutrophils; mDia1 is required for Hck membrane translocation, Hck activation, and Hck-mediated WASp tyrosine phosphorylation; mDia1-/- neutrophils show impaired Hck membrane targeting. |
Co-immunoprecipitation; mDia1-/- mouse neutrophils; immunofluorescence co-localization; Hck kinase activity assay; WASp phosphorylation western blot |
Biochemistry and cell biology |
Medium |
19234535
|
| 2009 |
mDia1 translocates to the platelet cytoskeleton following thrombin stimulation in a PI 3-kinase-dependent manner; mDia1 is required for thrombin-induced actin stress fiber formation and platelet spreading; PI 3-kinase promotes mDia1-RhoA interaction. |
Anti-mDia1 antibody loading; PI 3-kinase inhibitors; co-immunoprecipitation of mDia1-RhoA; actin staining; platelet spreading assay on fibrinogen |
Biochemical and biophysical research communications |
Medium |
19470376
|
| 2010 |
The cytoplasmic domain of RAGE (ctRAGE) contains an α-turn that mediates direct binding to mDia1; this ctRAGE-mDia1 interaction is essential for RAGE ligand-stimulated AKT phosphorylation and cell proliferation/migration. |
NMR solution structure of ctRAGE; NMR mapping of mDia1 binding interface; mutagenesis of α-turn; cell proliferation/migration assays |
The Journal of biological chemistry |
High |
22194616
|
| 2010 |
mDia1 targets v-Src to the cell periphery/focal adhesions via actin filament generation; mDia1-deficient cells show impaired membrane translocation of v-Src, reduced tyrosine phosphorylation, and suppressed transformation, tumorigenesis, and invasion. |
mDia1 knockout mouse embryonic fibroblasts transduced with temperature-sensitive v-Src; immunofluorescence of Src localization; focus formation; soft agar colony assay; nude mouse xenograft |
Molecular and cellular biology |
High |
20679479
|
| 2010 |
APC C-terminal basic domain nucleates actin filaments and synergizes with its in vivo binding partner mDia1 to overcome the dual cellular barrier imposed by profilin and capping protein; APC-mDia1 cooperation drives actin assembly in cells. |
In vitro pyrene-actin nucleation assays; EM of actin filaments; APC-mDia1 co-immunoprecipitation; cell-based actin assembly assay |
The Journal of cell biology |
High |
20566685
|
| 2010 |
mDia1 crystal structure of a complex between N-terminal (DID/GBD) and C-terminal (FH2+DAD) fragments reveals two models for autoinhibition in which DAD engagement by N-terminus is incompatible with actin filament formation; nearly full-length mDia1 is dimeric. |
X-ray crystallography; analytical ultracentrifugation/gel filtration (oligomeric state); in-solution biochemical characterization |
PloS one |
High |
20927338
|
| 2010 |
mDia1 rotates along the double helical strand of actin filament during processive elongation (helical rotation); this rotation is an intrinsic property of formins, independent of actin-bound nucleotide or profilin. |
Single-molecule fluorescence polarization of labeled F-actin elongating from immobilized mDia1; TIRF microscopy |
Science |
High |
21148346
|
| 2010 |
Flightless-I (Fli-I) directly binds mDia1, enhances its intrinsic actin assembly activity in vitro, promotes GTP-Rho-mediated relief of mDia1 autoinhibition, and is required for Daam1/mDia1-induced actin assembly in living cells. |
Direct binding assay (GST pull-down); in vitro pyrene-actin polymerization; RNAi knockdown in cells; constitutively active Rho rescue |
The Journal of biological chemistry |
High |
20223827
|
| 2010 |
ACTH-stimulated cortisol biosynthesis requires RhoA and DIAPH1 to mediate mitochondrial trafficking along microtubules; silencing DIAPH1 impairs mitochondrial movement and cortisol biosynthesis, increasing androgen secretion instead. |
Live cell video confocal microscopy; dominant-negative RhoA; DIAPH1 siRNA; cortisol/androgen secretion assays; co-immunoprecipitation of RhoA-DIAPH1 |
Endocrinology |
Medium |
20591975
|
| 2010 |
The Rho-mDia1 pathway is required for dendritic cell adhesion, spreading, invasive and directional migration, and sustained T-cell interaction/stimulation; mDia1-/- DCs show impaired cutaneous migration to draining lymph nodes in vivo. |
mDia1-/- mice; in vitro adhesion/spreading assay; Transwell invasion assay; in vivo FITC-induced DC migration; DC-T cell interaction assay |
Blood |
High |
20881208
|
| 2011 |
INF2, mDia1, and mDia2 all bind microtubules with high affinity via FH1-FH2-C constructs, but differ: mDia1 shows saturating binding at ~1:3 stoichiometry and is not a potent microtubule bundler; microtubule binding moderately inhibits mDia1 actin polymerization activity. |
In vitro microtubule co-sedimentation; TIRF microscopy; actin polymerization assay; stoichiometry analysis |
Molecular biology of the cell |
High |
21998204
|
| 2011 |
Rho-mDia1 activation causes Golgi fragmentation into ministacks via actin polymerization; mDia1 transiently localizes to Rab6-positive Golgi-derived transport vesicles and promotes their formation; Golgi fusion is repressed by active mDia1. |
Constitutively active mDia1 expression; LPA stimulation; live imaging of Golgi markers; cytoskeletal inhibitors (latrunculin B, blebbistatin, taxol); GFP-mDia1 localization |
Molecular biology of the cell |
Medium |
21680709
|
| 2011 |
mDia1 directly interacts with IRSp53 via IRSp53's SH3 domain and cooperates with WAVE2 to form filopodia; depletion of mDia1 or WAVE2 decreases IRSp53-induced filopodia formation; FRET confirms direct mDia1-IRSp53 interaction within filopodia. |
Co-immunoprecipitation; acceptor photobleaching FRET; siRNA knockdown; time-lapse live imaging |
The Journal of biological chemistry |
High |
22179776
|
| 2011 |
Rif GTPase induces filopodia via mDia1 (not mDia2), through a pathway independent of Cdc42 effectors N-WASP and IRSp53; FRET confirms direct Rif-mDia1 interaction within filopodia. |
RNAi knockdown; dominant-negative mDia1; acceptor photobleaching FRET; time-lapse imaging |
The Journal of biological chemistry |
Medium |
21339294
|
| 2012 |
Actin-capping protein induces stable detyrosinated microtubules in an mDia1-dependent manner by antagonizing mDia1 translocation on actin filament barbed ends, releasing mDia1 to act on microtubules. |
LatA/jasplakinolide treatment; mDia1 siRNA; capping protein siRNA; immunofluorescence of stable microtubules; live-cell mDia1 localization |
Molecular biology of the cell |
High |
22918941
|
| 2012 |
mDia1 is required for RAGE-ligand-induced c-Src membrane translocation, Rac1 activation, redox phosphorylation of AKT/GSK3β, and vascular smooth muscle cell migration; mDia1 loss reduces pathological neointimal expansion after injury in vivo. |
mDia1 siRNA/KO; mDia1-/- mice with femoral artery denudation; c-Src membrane fractionation; Rac1-GTP pull-down; AKT/GSK3β phosphorylation western blot |
Circulation research |
High |
22511750
|
| 2012 |
Abl kinases and mDia1 regulate caveolar domain organization and trafficking; mDia1 knockdown causes Cav1/caveolae clustering and prevents inward trafficking upon loss of adhesion; mDia1 acts downstream of Abl to control stress-fiber-linked Cav1 pool. |
mDia1 siRNA; constitutively active mDia1 rescue; live imaging of Cav1 and stress fibers; Abl-deficient cells |
Journal of cell science |
Medium |
22454521
|
| 2014 |
DIAPH1 (mDia1) negatively regulates megakaryocyte proplatelet formation by controlling actin and microtubule cytoskeleton dynamics; combined inhibition of DIAPH1 and ROCK/myosin II synergistically increases proplatelet formation. |
mDia1 knockout megakaryocytes; ROCK inhibitor; fluorescence microscopy of actin and microtubules; proplatelet formation quantification |
Blood |
High |
25298036
|
| 2014 |
mDia1 heterozygous and knockout granulocytes overexpress CD14 in a cell-autonomous manner, leading to hypersensitivity to LPS via CD14/TLR4 signaling; mDia1 deficiency downregulates membrane-associated genes specifically in granulocytes. |
mDia1 heterozygous and KO mice; flow cytometry; LPS stimulation assay; lenalidomide rescue; gene expression analysis |
Blood |
Medium |
24891322
|
| 2015 |
mDia1 acts as an EGF-regulated actin nucleator that polymerizes linear filaments to activate the Arp2/3 complex, cooperating sequentially with Arp2/3 to initiate lamellipodia and ruffles; this cooperation is required for cell migration. |
mDia1 knockdown and rescue; optogenetics; pharmacological Arp2/3 inhibition; live-cell imaging of ruffles; TIRF imaging |
Journal of cell science |
High |
26349808
|
| 2016 |
DIAPH1 R1213* gain-of-function variant (truncating the DAD C-terminus) disrupts DID-DAD autoinhibitory interaction, causing constitutive activation with increased cortical F-actin, stable microtubules in platelets, and reduced proplatelet formation from megakaryocytes. |
Exome sequencing; flow cytometry of platelet actin/tubulin; cultured megakaryocyte proplatelet formation; overexpression of R1213* in cells |
Blood |
High |
26912466
|
| 2016 |
DIAPH1 c.3610C>T mutation (R1204X, within the basic RRKR motif of DAD) disrupts the DID-DAD autoinhibitory interaction, producing constitutively active DIA1 with increased directional actin polymerization rates and elongated microvilli; mice expressing this mutant develop progressive deafness and stereocilia morphological abnormalities. |
DID-DAD binding assay; single-molecule imaging of actin polymerization velocity; transgenic mouse model; auditory brainstem response; scanning electron microscopy of stereocilia |
EMBO molecular medicine |
High |
27707755
|
| 2016 |
An mDia1-INF2 formin activation cascade, facilitated by IQGAP1 as a scaffold, is required for LPA-stimulated stable detyrosinated microtubule formation; mDia1 regulates INF2 localization to microtubules and their interaction is induced by LPA. |
siRNA knockdown of mDia1 and INF2; constitutively active formin mutants; IQGAP1 N-terminus direct binding to INF2 C-terminus (GST pull-down); immunofluorescence of Glu-MTs; co-immunoprecipitation |
Molecular biology of the cell |
High |
27030671
|
| 2016 |
Small molecule inhibitors of the ctRAGE-DIAPH1 interaction were identified by screening 58,000 compounds; these inhibitors suppress RAGE-dependent signaling and biological activities in vitro and in vivo, confirming that the ctRAGE-DIAPH1 protein-protein interaction is required for RAGE signal transduction. |
High-throughput small molecule screen; NMR competition assay; X-ray crystallization of RAGE domains; cellular signaling assays; in vivo pharmacology |
Scientific reports |
High |
26936329
|
| 2018 |
Helical rotation of mDia1 during processive actin elongation converts F-actin into a form resistant to cofilin binding and severing by untwisting the long-pitch actin helix; tethered (non-rotatable) mDia1 generates more cofilin-resistant F-actin in cells. |
Single-molecule fluorescence polarization; electron microscopy of F-actin twist; constitutively active tethered mDia1 mutant overexpression; cofilin-F-actin severing and binding assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
29760064
|
| 2018 |
mDia1 and mDia3 together generate a dynamic cortical F-actin meshwork in Sertoli cells that is continuous with contractile actomyosin bundles and is required for Sertoli-germ cell interaction and spermatogenesis; mDia1/3 loss induces ectopic espin1-containing F-actin bundles. |
mDia1/mDia3 double knockout mice; superresolution and single-molecule imaging; spermatogenesis phenotyping; immunostaining of F-actin architectures |
PLoS biology |
High |
30256801
|
| 2018 |
Diaph1 (mDia1) promotes TGFβ receptor II (TβRII) endocytosis and intracellular trafficking in hepatic stellate cells by interacting directly with both TβRII and Rab5a; Diaph1 increases Rab5a GTPase activity; Diaph1 inactivation blocks SMAD3 phosphorylation and myofibroblastic activation. |
shRNA knockdown; SMIFH2 inhibitor; co-immunoprecipitation of Diaph1-TβRII and Diaph1-Rab5a; active/inactive Rab5a mutants; endosomal localization assay; tumor implantation model |
FASEB journal |
High |
32304339
|
| 2018 |
BIG2-ARF1-RhoA-mDia1 signaling axis regulates dendritic Golgi polarization and dendrite growth/maintenance in hippocampal neurons; mDia1 acts as downstream effector of RhoA in this pathway. |
shRNA knockdown; constitutively active ARF1/RhoA mutants; LPA treatment; immunofluorescence of Golgi markers; in utero electroporation |
Molecular neurobiology |
Medium |
29455446
|
| 2019 |
Cdk1 phosphorylates DIAPH1, preventing profilin1 binding, to maintain metaphase cortical tension; DIAPH1 phosphorylation is required for kinetochore stretching and spindle assembly checkpoint (SAC) inactivation at anaphase onset. |
Cdk1 phosphorylation site mutants of DIAPH1; profilin1 binding assay; cortical tension measurement; SAC activation assay; intra-kinetochore distance measurement; live-cell imaging |
Nature communications |
High |
30816115
|
| 2020 |
SPIN90 forms a ternary complex with Arp2/3 and mDia1, efficiently recruiting mDia1 to SPIN90-Arp2/3 nucleated filament pointed ends; this greatly enhances nucleation and yields rapidly elongating unbranched filaments, shifting cortical actin toward a formin-dominated network. |
In vitro reconstitution; TIRF microscopy; biochemical pull-down; in-cell actin network analysis |
Nature cell biology |
High |
32572169
|
| 2020 |
mDia1 and mDia3 localize to the immune synapse upon TCR activation and are required for formin-mediated actin polymerization at the synapse, which spatiotemporally controls LAT phosphorylation by Zap70. |
mDia1 and mDia3 knockout mice; pharmacological formin inhibition; high-resolution imaging and 3D reconstruction of immune synapse; LAT and Zap70 phosphorylation assays |
Science advances |
High |
31911947
|
| 2021 |
Loss of DIAPH1 causes mitochondrial respiratory chain complex IV dysfunction and combined immune deficiency, including defective lymphocyte maturation, poor T-cell activation, and inefficient MTOC repositioning to the immunological synapse. |
CRISPR-Cas9 DIAPH1 KO in PBMCs; patient-derived T cell assays; immunophenotyping by flow cytometry; mitochondrial complex IV activity assay; immunofluorescence of MTOC repositioning |
The Journal of allergy and clinical immunology |
High |
33662367
|
| 2021 |
Tension-controlled actin polymerization at focal adhesions requires mDia1 and exhibits pulsatile dynamics triggered by contractile forces; suppression of mDia1-mediated actin polymerization increases stress fiber tension, raising the frequency of spontaneous SF damage and decreasing zyxin-mediated SF repair. |
Live-cell imaging of mDia1 at focal adhesions; traction force microscopy; mathematical modeling; mDia1 knockdown; stress fiber damage frequency quantification |
Developmental cell |
High |
34822787
|
| 2021 |
Small-molecule antagonists of ctRAGE-DIAPH1 interaction (RAGE229) suppress RAGE-DIAPH1 binding (confirmed by FRET and NMR), reduce diabetic complications in mice including nephropathy and inflammation, without lowering blood glucose. |
NMR spectroscopy mapping of compound binding site; FRET; in vivo diabetic mouse models (STZ); histopathology; inflammatory cytokine measurement |
Science translational medicine |
High |
34818060
|
| 2023 |
DIAPH1 mediates RAGE-dependent atherosclerosis progression and regulates hepatic lipid metabolism; DIAPH1 deletion reduces atherosclerosis and plasma cholesterol/triglycerides; DIAPH1 promotes SREBP1 nuclear translocation via the actin cytoskeleton, independently of canonical insulin/carbohydrate signaling. |
Ldlr-/- Diaph1-/- double-KO mice; Western diet feeding; lipid/cholesterol measurement; hepatic gene expression; SREBP1 nuclear translocation assay; actin cytoskeleton perturbation |
Communications biology |
High |
36932214
|