Affinage

MACF1

Microtubule-actin cross-linking factor 1, isoforms 1/2/3/4/5 · UniProt Q9UPN3

Length
7388 aa
Mass
838.3 kDa
Annotated
2026-04-28
77 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MACF1 (also called ACF7) is a giant spectraplakin that crosslinks the actin and microtubule cytoskeletons to coordinate cell polarity, migration, and differentiation across diverse tissues. Its N-terminal calponin homology domains bind F-actin (regulated by Src/FAK phosphorylation) while its C-terminal GAR and GSR domains bind and bundle microtubules (regulated by GSK3β phosphorylation downstream of Wnt); an intrinsic ATPase activity guides microtubule plus ends along actin filaments toward focal adhesions, and interaction with CAMSAP3 anchors noncentrosomal microtubule minus ends to establish epithelial apico-basal polarity (PMID:10601340, PMID:18854161, PMID:21295697, PMID:27802168). MACF1 also functions as a scaffold in canonical Wnt signaling by associating with the Axin/β-catenin/GSK3β/APC destruction complex and mediating its Wnt-dependent translocation to LRP6, and it is required for ciliogenesis through interaction with ciliary proteins MKKS and TALPID3 (PMID:16815997, PMID:27783952). De novo missense variants in the GAR or EF-hand domains cause lissencephaly and brain malformations through gain-of-function increased microtubule binding, while bi-allelic variants in the Plakin domain cause a distinct complex neurodevelopmental syndrome (PMID:30471716, PMID:40925378).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1999 High

    Establishing that MACF1 is a bona fide actin–microtubule crosslinker resolved the fundamental question of whether a single molecule could simultaneously engage both cytoskeletal systems.

    Evidence In vitro binding assays and co-localization in transfected cells demonstrated separable N-terminal actin-binding and C-terminal MT-binding domains

    PMID:10601340

    Open questions at the time
    • Full-length protein binding stoichiometry unknown
    • No functional phenotype yet established
  2. 2001 High

    Dissecting the C-terminal MT-binding region into GAR (binding/stabilizing) and GSR (bundling) sub-domains revealed that MACF1 uses two distinct mechanisms to engage microtubules.

    Evidence Domain deletions tested by transfection and in vitro MT-binding/bundling assays

    PMID:11112700

    Open questions at the time
    • Structural basis of GAR and GSR recognition of MTs unresolved
    • Physiological relevance of MT bundling activity not tested in vivo
  3. 2003 High

    Conditional knockout demonstrated that MACF1 is the essential molecule that guides MT plus-end growth along polarized actin to cortical sites, answering how cells coordinate the two cytoskeletons for polarized migration.

    Evidence Genetic KO in endodermal cells with live-cell imaging; rescue required both actin- and MT-binding domains

    PMID:14636561

    Open questions at the time
    • Mechanism of plus-end tracking not yet explained
    • Upstream signals controlling MACF1 cortical localization unknown
  4. 2004 High

    Identification of p230/Golgin-245 as a MACF1 binding partner linked the crosslinker to Golgi-to-surface transport of GPI-anchored proteins, revealing a cargo-selective trafficking role.

    Evidence Yeast two-hybrid, Co-IP, in vitro binding, and GPI-AP trafficking assays

    PMID:15265687

    Open questions at the time
    • Whether MACF1 physically accompanies vesicles or merely organizes tracks is unknown
    • Specificity for GPI-APs over other cargoes not mechanistically explained
  5. 2006 High

    Discovery that MACF1 scaffolds the Axin/β-catenin/GSK3β destruction complex and translocates it to LRP6 upon Wnt stimulation established an unexpected role for a cytoskeletal crosslinker in canonical Wnt signal transduction.

    Evidence Reciprocal Co-IP, TCF/β-catenin reporter assays, dominant-negative constructs, and MACF1-null mouse phenocopying Wnt3/LRP5/6 double KO

    PMID:16815997

    Open questions at the time
    • Which MACF1 domain mediates Axin interaction not mapped
    • Whether cytoskeletal crosslinking and Wnt scaffolding are mechanistically coupled is unclear
  6. 2007 High

    Direct binding of the MACF1 actin-binding domain to Rapsyn at the neuromuscular junction extended MACF1's role to synaptic organization, linking cytoskeletal scaffolding to receptor clustering.

    Evidence Co-IP, SPR, and blot overlay confirmed direct interaction with Rapsyn TPR domains

    PMID:17222516

    Open questions at the time
    • Functional consequence of MACF1-Rapsyn disruption at NMJ not yet shown genetically
  7. 2008 High

    Identification of an intrinsic actin-regulated ATPase activity in MACF1 revealed that crosslinking alone is insufficient — active energy-dependent motility is required to target MTs along F-actin to focal adhesions.

    Evidence In vitro ATPase assay, conditional epidermal KO, domain-specific rescue experiments, and live-cell focal adhesion dynamics imaging

    PMID:18854161

    Open questions at the time
    • ATPase domain identity and structural basis not determined
    • Whether ATPase drives processive movement or conformational cycling unknown
  8. 2009 Medium

    Demonstrating separate requirements for actin/MT-binding (axonal MT organization) and EF-hand/eIF5C interaction (filopodia formation) in neurons revealed MACF1 executes mechanistically distinct functions within a single cell type.

    Evidence Domain deletions and Co-IP of eIF5C in neuronal culture systems; Drosophila Shot ortholog used for cross-species validation

    PMID:19571116

    Open questions at the time
    • eIF5C interaction confirmed only by single Co-IP
    • Translational regulation link not mechanistically elaborated
  9. 2010 High

    Placing MACF1 downstream of ErbB2→Memo→RhoA/mDia1→GSK3 inhibition established how receptor tyrosine kinase signaling recruits MACF1 to the membrane for MT capture during directed migration.

    Evidence Systematic shRNA knockdown of pathway components with MT capture as readout, rescue experiments

    PMID:20937854

    Open questions at the time
    • Direct binding between pathway components and MACF1 not demonstrated
    • Whether this pathway operates in non-breast epithelial contexts unknown
  10. 2011 High

    Direct phosphorylation of MACF1's MT-binding domain by GSK3β, inhibited by Wnt, explained how dynamic phospho-cycling controls polarized MT guidance — constitutive engagement restores MT architecture but not directionality.

    Evidence In vitro kinase assay, phospho-site mapping, phospho-mutant rescue in ACF7-null keratinocytes, in vivo wound-repair model

    PMID:21295697

    Open questions at the time
    • Number and identity of all functionally relevant phospho-sites not exhaustively mapped
    • How phospho-cycling is spatially restricted within the cell unknown
  11. 2012 Medium

    ELMO/DOCK180-mediated recruitment of MACF1 to the membrane via a polyproline–spectrin repeat interaction identified an alternative, integrin-triggered pathway for MT capture distinct from the ErbB2 pathway.

    Evidence Co-IP with domain mapping, live-cell MT capture imaging, integrin-mediated spreading assays

    PMID:23184944

    Open questions at the time
    • Single lab finding; independent replication not reported
    • Relationship between ELMO and ErbB2 recruitment pathways not clarified
  12. 2014 High

    Conditional KO in developing cortical neurons established that MACF1 is essential for radial neuronal migration through GSK3-regulated microtubule stabilization, extending the GSK3β–MACF1 axis to brain development.

    Evidence Conditional KO with in utero electroporation, Co-IP for GSK3 interaction, live neuron migration imaging

    PMID:25224226

    Open questions at the time
    • Whether GSK3 phosphorylates the same sites in neurons as in keratinocytes not confirmed
    • Contributions of other spectraplakins not excluded
  13. 2016 High

    Multiple 2016 discoveries collectively resolved MACF1's structural basis and expanded its functional repertoire: crystal structures of the N-terminal and C-terminal domains revealed how Src/FAK phosphorylation activates actin binding and how the GAR domain coordinates Zn²⁺ for MT binding; CAMSAP3 interaction anchored noncentrosomal MT minus ends for epithelial polarity; and interaction with MKKS/TALPID3 established a requirement for ciliogenesis.

    Evidence X-ray crystallography of NT and EF1-EF2-GAR domains, phospho-mutant rescue in vivo, Co-IP of CAMSAP3 and ciliary proteins, CRISPR KO in epithelial and retinal systems

    PMID:27216888 PMID:27693509 PMID:27783952 PMID:27802168 PMID:28602822

    Open questions at the time
    • Full-length MACF1 structure unavailable
    • How MACF1 coordinates CAMSAP3 binding with plus-end tracking mechanistically unresolved
    • Structural basis of MKKS/TALPID3 interaction unknown
  14. 2017 High

    Tissue-specific KO studies demonstrated MACF1's requirement for intestinal wound healing and GABAergic interneuron migration, broadening the phenotypic landscape and confirming MT stabilization as the common downstream mechanism.

    Evidence Conditional intestinal KO with colitis model; conditional brain KO with two independent Cre drivers for interneuron analysis

    PMID:27756764 PMID:28541346

    Open questions at the time
    • Whether intestinal and neuronal phenotypes involve identical molecular pathways unknown
    • Compensatory mechanisms in heterozygous animals not characterized
  15. 2017 High

    In zebrafish oocytes, MACF1's actin-binding domain was shown to link cortical actin to the Balbiani body for animal-vegetal axis establishment, extending MACF1's role to oocyte polarity.

    Evidence Endogenous CRISPR domain deletion and live imaging in zebrafish oocytes

    PMID:28880872

    Open questions at the time
    • Whether mammalian oocytes use MACF1 for similar polarity establishment unknown
  16. 2018 High

    Identification of HectD1 as the E3 ubiquitin ligase targeting MACF1 for proteasomal degradation revealed a post-translational control mechanism; MACF1 protein stability promotes EMT and migration.

    Evidence Ubiquitination assays, proteasome inhibitor rescue, shRNA screens, in vivo metastasis models

    PMID:29386124

    Open questions at the time
    • Specific ubiquitination sites on MACF1 not mapped
    • Whether HectD1 and USP14 compete at the same ubiquitin chains unclear
  17. 2018 Medium

    Clinical genetics linked de novo GAR-domain variants to lissencephaly with pontine malformation and shortened cilia, providing the first human disease association and supporting the ciliary function.

    Evidence Whole-exome/genome sequencing in affected families plus ciliogenesis assay in patient-derived cells

    PMID:30471716

    Open questions at the time
    • Functional rescue not performed
    • Mechanism of cilia shortening by GAR variants not elucidated at molecular level
  18. 2019 High

    NMJ-specific analysis confirmed that MACF1 organizes a cytoskeletal scaffold at the synapse (recruiting EB1, MAP1b, Vinculin via Rapsyn), and its loss impairs synaptic transmission, closing the loop opened by the 2007 Rapsyn binding discovery.

    Evidence Co-IP/MS, conditional NMJ analysis, electrophysiology

    PMID:30842214

    Open questions at the time
    • Whether MACF1 loss causes NMJ disease in humans unknown
    • Relative contributions of MT vs actin scaffolding at NMJ not separated
  19. 2021 High

    Multiple discoveries in 2021 established MACF1 as a regulator of myonuclei positioning in muscle, identified USP14 as a stabilizing deubiquitinase opposing HectD1, and revealed cytoplasmic sequestration of transcriptional repressors TCF12/E2F6 as a mechanism for promoting osteoblast differentiation.

    Evidence Conditional muscle KO in mouse and Drosophila; Co-IP/ubiquitination assays for USP14; Co-IP and nuclear-cytoplasmic fractionation for TCF12/E2F6

    PMID:33664480 PMID:33737492 PMID:34448452

    Open questions at the time
    • USP14 interaction confirmed in single lab only
    • TCF12/E2F6 sequestration mechanism is correlative — no structural basis
    • Whether myonuclei mispositioning causes functional myopathy not established
  20. 2025 High

    Expanding the genotype-phenotype map revealed that EF-hand domain variants cause brain malformation through gain-of-function increased MT binding, while bi-allelic Plakin domain variants cause a distinct neurodevelopmental syndrome, establishing domain-specific pathomechanisms.

    Evidence WES/WGS, MT co-sedimentation assays for EF-hand mutants, RNA-seq and ChIP of human fetal brain for isoform characterization

    PMID:40925378

    Open questions at the time
    • Animal model validation of EF-hand gain-of-function variants not reported
    • Mechanism by which Plakin domain variants cause disease not functionally characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structural model of MACF1 is lacking, and it remains unknown how its multiple functional domains are spatially coordinated, how its ATPase activity is structurally organized, and how tissue-specific isoforms dictate distinct cellular functions.
  • No full-length cryo-EM or AlphaFold-validated structure
  • ATPase domain identity and catalytic mechanism unresolved
  • Isoform-specific functions in different tissues not systematically compared

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0098772 molecular function regulator activity 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005856 cytoskeleton 5 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005929 cilium 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 2 R-HSA-1500931 Cell-Cell communication 1
Partners
AXIN1CAMSAP3ELMO1GOLGA4GSK3BHECTD1RAPSNUSP14
Complex memberships
Wnt destruction complex (Axin/β-catenin/GSK3β/APC)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 MACF1 (mACF7) contains a functional N-terminal actin-binding domain and a C-terminal domain that interacts with and stabilizes microtubules, allowing the full-length protein to associate with both actin and microtubules simultaneously in transfected cells and in vitro. In vitro binding assays, transient transfection, co-localization with cytoskeletal markers The Journal of cell biology High 10601340
2001 The C-terminal microtubule-binding domain of MACF1 contains at least two distinct MT-binding regions: a GAR domain that binds and partially stabilizes MTs, and a GSR-repeat domain that bundles MTs; together they bundle MTs and confer nocodazole resistance. Transient transfection studies and in vitro MT-binding assays Journal of cell science High 11112700
2003 ACF7 (MACF1) acts as an essential integrator of microtubule-actin dynamics: it binds along microtubules and concentrates at their distal ends and cortical actin-rich sites; in its absence, MTs no longer grow along polarized actin bundles or pause/tether at cortical sites, resulting in unstable MTs, skewed trajectories, and failure to sustain polarization and coordinated migration. Rescue requires both actin- and microtubule-binding domains. Conditional knockout in endodermal cells, live-cell imaging, rescue with domain mutants Cell High 14636561
2006 MACF1 participates in canonical Wnt signaling: in the absence of Wnt, MACF1 associates with an Axin/β-catenin/GSK3β/APC destruction complex; upon Wnt stimulation, MACF1 mediates translocation of the Axin complex to LRP6 at the plasma membrane. MACF1 knockdown reduces nuclear β-catenin and TCF/β-catenin-dependent transcription. MACF1-null mice die at gastrulation with phenotypes resembling Wnt-3 and LRP5/6 double knockouts. Co-immunoprecipitation, siRNA knockdown, dominant-negative constructs, TCF/β-catenin reporter assay, MACF1 knockout mouse Genes & development High 16815997
2007 The N-terminal actin-binding domain of ACF7 (MACF1) directly binds to the tetratricopeptide repeat (TPR) domains of rapsyn at the neuromuscular junction, as demonstrated by co-expression in fibroblasts, co-immunoprecipitation, surface plasmon resonance, and blot overlay assays. Co-immunoprecipitation, surface plasmon resonance, blot overlay, confocal co-localization Neuroscience High 17222516
2008 ACF7 (MACF1) possesses an intrinsic actin-regulated ATPase domain that is functionally required, beyond the F-actin, MT, and MT plus-end binding domains, for targeting microtubules along F-actin to focal adhesions, regulating focal adhesion-cytoskeletal dynamics, and enabling directed epidermal cell migration. Conditional knockout in skin epidermis, domain rescue experiments, in vitro ATPase assay, live-cell imaging of focal adhesion dynamics Cell High 18854161
2004 MACF1 interacts with the TGN protein p230/Golgin-245 through its C-terminal domain (binding the N-terminal flexible end of p230), and this interaction is required for transport of GPI-anchored proteins (but not transmembrane proteins) from the TGN to the cell periphery along microtubule and actin tracts. Yeast two-hybrid, co-immunoprecipitation, in vitro binding assay, dominant-negative expression of interacting domains, YFP-SP-GPI trafficking assay Experimental cell research High 15265687
2010 ErbB2 receptor recruits ACF7 to the plasma membrane via a signaling pathway involving Memo, RhoA/mDia1, and GSK3 inhibition, and ACF7 localization to the plasma membrane is both necessary and sufficient for microtubule capture and stabilization downstream of ErbB2-induced cell migration. shRNA knockdown, dominant-negative and constitutively active constructs, immunofluorescence, live-cell MT tracking, rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 20937854
2011 GSK3β directly phosphorylates ACF7 at residues within its microtubule-binding domain, uncoupling ACF7 from microtubules; Wnt signaling inhibits GSK3β, allowing ACF7-microtubule engagement. Phosphorylation-refractile ACF7 restores overall MT architecture but not polarized movement; dynamic phospho-regulation is required for stem cell directed migration and wound repair. In vitro kinase assay (GSK3β phosphorylation of ACF7), phospho-mutant rescue in ACF7-null keratinocytes, live-cell MT imaging, hair follicle SC wound-healing model Cell High 21295697
2009 ACF7 (and its Drosophila ortholog Shot) regulates neuronal microtubule organization (requiring both F-actin and MT binding domains) and controls filopodia formation in axonal growth cones (requiring EF-hand motifs and interaction with the translational regulator Krasavietz/eIF5C), establishing two mechanistically distinct cytoskeletal roles in axon extension. Neuronal culture systems with ACF7 knockdown/overexpression, domain deletion constructs, co-immunoprecipitation (ACF7-eIF5C interaction), live imaging of growth cones Journal of cell science Medium 19571116
2012 ELMO directly interacts with ACF7 via a C-terminal polyproline segment in ELMO and the last spectrin repeat of ACF7; ELMO recruits ACF7 to the membrane to promote microtubule capture and stability, increasing persistence of cellular protrusions; this function requires the Rac GEF DOCK180. Co-immunoprecipitation, direct domain interaction mapping, live-cell imaging of MT capture, integrin-mediated cell spreading assays The Journal of biological chemistry Medium 23184944
2014 MACF1 regulates cortical pyramidal neuron migration by controlling microtubule dynamics and mediating GSK-3 signaling in developing neurons; MACF1 deletion causes aberrant neuronal positioning, abnormal leading process and centrosome dynamics, and reduced microtubule stability. MACF1 interacts with GSK-3 in developing neurons. Conditional knockout (floxed allele + in utero electroporation), co-immunoprecipitation (MACF1-GSK3), live imaging of neuron migration, MT stability assays Developmental biology High 25224226
2016 Src/FAK complex phosphorylates a key tyrosine residue in the calponin homology (CH) domain of ACF7's N-terminal domain, and this phosphorylation is essential for F-actin binding of ACF7 and for focal adhesion dynamics and epidermal migration in vitro and in vivo. Crystal structure of the ACF7 NT domain was resolved to inform this mechanism. X-ray crystallography of ACF7 NT domain (2.x Å), phospho-mutant rescue, Src/FAK kinase assay, in vitro and in vivo (skin epidermis) migration assays Nature communications High 27216888
2016 ACF7 (MACF1) specifically binds CAMSAP3 and is required for apical localization of CAMSAP3-decorated microtubule minus ends in intestinal epithelial cells; loss of ACF7 impairs formation of polarized epithelial cysts and disrupts apico-basal polarity. Co-immunoprecipitation (ACF7-CAMSAP3), CRISPR/RNAi knockouts, 3D epithelial cyst assays, immunofluorescence of microtubule minus-end organization Journal of cell science High 27802168
2016 In Caco2 epithelial cells, ACF7 interacts with CAMSAP3 (Nezha) at the minus ends of noncentrosomal microtubules and anchors them to actin filaments; these minus-end MTs cooperate with actin retrograde flow to maintain MT orientation perpendicular to the cell edge and regulate focal adhesion size and cell migration. Co-immunoprecipitation, MT minus-end tracking, focal adhesion size quantification, migration assays, knockdown experiments Developmental cell High 27693509
2016 MACF1 is required for ciliogenesis: MACF1 ablation in the developing retina abolishes ciliogenesis, prevents basal body docking to ciliary vesicles, and blocks apical migration; MACF1 interacts with ciliary proteins MKKS and TALPID3, suggesting it coordinates microtubule-to-actin trafficking required for ciliogenesis. Conditional knockout (retina-specific), co-immunoprecipitation (MACF1-MKKS, MACF1-TALPID3), electron microscopy, immunofluorescence of cilia and basal bodies Cell reports High 27783952
2017 ACF7 loss leads to aberrant microtubule organization, tight junction stabilization, and impaired wound closure in intestinal epithelium; ablation of ACF7 in mice inhibits intestinal wound healing and increases susceptibility to experimental colitis. Conditional intestinal KO, wound scratch assays, immunofluorescence of tight junction proteins and MTs, experimental colitis model Nature communications High 28541346
2017 The 2.8 Å crystal structure of the hACF7 EF1-EF2-GAR MT-binding module revealed that the EF1-EF2 domain is an EFβ-scaffold with two Ca2+ ions and the GAR domain has a unique α/β sandwich fold coordinating Zn2+; the GAR domain alone is sufficient for MT binding via a conserved basic patch distal to the Zn2+-binding site, while EF1-EF2 alone is insufficient. X-ray crystallography (2.8 Å), domain deletion/mutagenesis, MT-binding assays Structure High 28602822
2018 The E3 ubiquitin ligase HectD1 targets ACF7 for proteasome-mediated degradation; HectD1 depletion stabilizes ACF7, promoting EMT and cell migration. ACF7 is essential for maintenance of the EMT program. shRNA screens, ubiquitination assays, proteasome inhibitor rescue, mouse metastasis models, breast cancer patient biopsies Cell reports High 29386124
2018 MACF1 variants encoding zinc-binding residues in the GAR (microtubule-binding) domain cause a distinctive lissencephaly and brainstem malformation with absent pontine crossing fibers, and affected cells show increased proportions of short cilia. Whole-exome/genome sequencing (clinical), ciliogenesis assay in patient cells American journal of human genetics Medium 30471716
2019 MACF1 is concentrated at neuromuscular synapses where it binds Rapsyn and serves as a synaptic organizer for MT-associated proteins EB1 and MAP1b and actin-associated protein Vinculin; MACF1 deficiency impairs synaptic differentiation and transmission in mice. Co-immunoprecipitation with AChRs/Rapsyn, mass spectrometry, conditional NMJ-specific analysis, electrophysiology The Journal of cell biology High 30842214
2017 MACF1 regulates GABAergic interneuron migration and positioning in the developing mouse brain; conditional MACF1 deletion reduces interneuron numbers and disrupts positioning, speed, and mode of migration, associated with decreased microtubule stability in interneurons. Conditional KO (Dlx5/6-Cre and Nkx2.1-Cre), in vivo migration tracking, MT stability assays, morphometric analysis Cerebral cortex High 27756764
2017 In zebrafish oocytes, Macf1a localizes to the Balbiani body and mediates its dissociation via its actin-binding domain (ABD); the ABD (not the plectin repeat domain) is required for linking cortical actin to the Balbiani body mRNP granule to drive its dissociation and nuclear positioning, establishing animal-vegetal polarity. CRISPR/Cas9 endogenous domain deletion, live imaging, pharmacological disruption of actin/MTs PLoS genetics High 28880872
2019 Deficiency of MACF1 in osteoblasts attenuates BMP2/Smad/Runx2 signaling, inhibiting osteoblast differentiation and bone formation in vivo. Conditional KO (Osx-Cre), primary osteoblast differentiation assays, micro-CT, western blotting for Smad/Runx2 pathway Journal of cellular and molecular medicine Medium 31709715
2020 MACF1 directly interacts with SMAD7 and facilitates SMAD7 nuclear translocation to initiate downstream osteogenic pathways; mesenchymal-specific MACF1 deletion reduces nuclear SMAD7 and attenuates bone formation. Co-immunoprecipitation (MACF1-SMAD7 direct interaction), nuclear-cytoplasmic fractionation, conditional KO (Prrx1-Cre), bone histomorphometry Cells Medium 32143362
2021 MACF1 is an essential regulator of myonuclei positioning in skeletal muscle: it controls microtubule dynamics and density around myonuclei, regulates myonuclei motion, and its conditional muscle-specific KO causes extra-synaptic myonuclei mispositioning, NMJ fragmentation, and increased mitochondrial biogenesis. Conditional muscle-specific KO (mouse), Drosophila muscle genetics, in vitro myotube microtubule dynamics, electron microscopy of triads, calcium release assays eLife High 34448452
2021 MACF1 interacts with transcription factors TCF12 and E2F6 (repressors of osteoblast differentiation) and with CDK12 and MEAF6; MACF1 sequesters TCF12 and E2F6 in the cytoplasm in a concentration-dependent manner, preventing their nuclear repressor activity and thereby promoting osteoblast differentiation. Co-immunoprecipitation (MACF1 with TCF12, E2F6, CDK12, MEAF6), nuclear-cytoplasmic fractionation, transcriptome analysis, knockdown/overexpression Cell death and differentiation Medium 33664480
2021 USP14 is a deubiquitinating enzyme that directly associates with ACF7 and inhibits its proteasomal degradation by removing ubiquitin; USP14-mediated stabilization of ACF7 promotes NSCLC cell migration. Proteomic identification (Co-IP/MS), co-immunoprecipitation, ubiquitination assay, knockdown/overexpression of USP14, migration assay Journal of biosciences Medium 33737492
2021 MACF1 promotes osteoblastic cell migration by stabilizing microtubules and increasing total MAP1B mRNA expression through TCF7 transcriptional activity, while also decreasing GSK3β-mediated phosphorylation of MAP1B at T1265, thereby regulating MAP1B activity downstream of the GSK3β pathway. siRNA knockdown, luciferase reporter assay, ChIP (TCF7 binding to Map1b promoter), in vitro and in vivo migration assays, GSK3β inhibitor (LiCl) Bone Medium 34700040
2025 De novo heterozygous missense variants in the EF-hand domains of MACF1 (in addition to the GAR domain) cause brain malformation; experimental evidence shows that EF-hand/GAR module variants increase microtubule binding, indicating a toxic gain-of-function mechanism. Bi-allelic non-GAR domain variants (mainly Plakin domain) cause a distinct complex neurodevelopmental syndrome. Whole-exome/genome sequencing, MT co-sedimentation/binding assays for EF-hand mutants, RNA-seq and ChIP of human fetal brain tissue for isoform characterization American journal of human genetics High 40925378

Source papers

Stage 0 corpus · 77 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 ACF7: an essential integrator of microtubule dynamics. Cell 262 14636561
2008 ACF7 regulates cytoskeletal-focal adhesion dynamics and migration and has ATPase activity. Cell 227 18854161
1999 Microtubule actin cross-linking factor (MACF): a hybrid of dystonin and dystrophin that can interact with the actin and microtubule cytoskeletons. The Journal of cell biology 187 10601340
2006 The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway. Genes & development 158 16815997
2011 Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β. Cell 155 21295697
2001 Characterization of the microtubule binding domain of microtubule actin crosslinking factor (MACF): identification of a novel group of microtubule associated proteins. Journal of cell science 137 11112700
2009 Mouse ACF7 and drosophila short stop modulate filopodia formation and microtubule organisation during neuronal growth. Journal of cell science 105 19571116
2010 ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells. Proceedings of the National Academy of Sciences of the United States of America 91 20937854
2014 MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling. Developmental biology 78 25224226
2016 Control of apico-basal epithelial polarity by the microtubule minus-end-binding protein CAMSAP3 and spectraplakin ACF7. Journal of cell science 70 27802168
1996 Cloning and characterization of mouse ACF7, a novel member of the dystonin subfamily of actin binding proteins. Genomics 70 8954775
2018 MACF1 Mutations Encoding Highly Conserved Zinc-Binding Residues of the GAR Domain Cause Defects in Neuronal Migration and Axon Guidance. American journal of human genetics 66 30471716
2004 Interaction between p230 and MACF1 is associated with transport of a glycosyl phosphatidyl inositol-anchored protein from the Golgi to the cell periphery. Experimental cell research 64 15265687
2016 Bioactive Flavonoids, Antioxidant Behaviour, and Cytoprotective Effects of Dried Grapefruit Peels (Citrus paradisi Macf.). Oxidative medicine and cellular longevity 53 26904169
2016 The CAMSAP3-ACF7 Complex Couples Noncentrosomal Microtubules with Actin Filaments to Coordinate Their Dynamics. Developmental cell 51 27693509
2016 In vivo epidermal migration requires focal adhesion targeting of ACF7. Nature communications 46 27216888
2000 Acf7 (MACF) is an actin and microtubule linker protein whose expression predominates in neural, muscle, and lung development. Developmental dynamics : an official publication of the American Association of Anatomists 45 11002341
2019 MACF1 links Rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses. The Journal of cell biology 42 30842214
2018 The E3 Ubiquitin Ligase HectD1 Suppresses EMT and Metastasis by Targeting the +TIP ACF7 for Degradation. Cell reports 40 29386124
2016 Isoforms, structures, and functions of versatile spectraplakin MACF1. BMB reports 40 26521939
2007 The actin binding domain of ACF7 binds directly to the tetratricopeptide repeat domains of rapsyn. Neuroscience 40 17222516
2001 Novel alternative splicings of BPAG1 (bullous pemphigoid antigen 1) including the domain structure closely related to MACF (microtubule actin cross-linking factor). The Journal of biological chemistry 40 11751855
2017 The role of MACF1 in nervous system development and maintenance. Seminars in cell & developmental biology 39 28579452
2012 ELMO recruits actin cross-linking family 7 (ACF7) at the cell membrane for microtubule capture and stabilization of cellular protrusions. The Journal of biological chemistry 39 23184944
2019 Deficiency of Macf1 in osterix expressing cells decreases bone formation by Bmp2/Smad/Runx2 pathway. Journal of cellular and molecular medicine 37 31709715
2016 Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina. Cell reports 35 27783952
2009 Large gradient high magnetic field affects the association of MACF1 with actin and microtubule cytoskeleton. Bioelectromagnetics 34 19475564
2001 MACF1 gene structure: a hybrid of plectin and dystrophin. Mammalian genome : official journal of the International Mammalian Genome Society 33 11845288
2018 High fat diet exacerbates intestinal barrier dysfunction and changes gut microbiota in intestinal-specific ACF7 knockout mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 30530289
2014 ACF7 is a hair-bundle antecedent, positioned to integrate cuticular plate actin and somatic tubulin. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 24381291
2017 MACF1, versatility in tissue-specific function and in human disease. Seminars in cell & developmental biology 31 28577926
2017 Microtubule-actin crosslinking factor 1 (Macf1) domain function in Balbiani body dissociation and nuclear positioning. PLoS genetics 31 28880872
2017 ACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics. Nature communications 30 28541346
2023 MACF1 overexpression in BMSCs alleviates senile osteoporosis in mice through TCF4/miR-335-5p signaling pathway. Journal of orthopaedic translation 29 36969134
2017 MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice. Cerebral cortex (New York, N.Y. : 1991) 29 27756764
2021 Strength Through Unity: The Power of the Mega-Scaffold MACF1. Frontiers in cell and developmental biology 24 33816492
2020 Mesenchymal MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation. Cells 24 32143362
2016 Genetic Variants of Microtubule Actin Cross-linking Factor 1 (MACF1) Confer Risk for Parkinson's Disease. Molecular neurobiology 24 27021023
2018 MACF1 Overexpression by Transfecting the 21 kbp Large Plasmid PEGFP-C1A-ACF7 Promotes Osteoblast Differentiation and Bone Formation. Human gene therapy 23 29334773
2016 Variation in Key Flavonoid Biosynthetic Enzymes and Phytochemicals in 'Rio Red' Grapefruit (Citrus paradisi Macf.) during Fruit Development. Journal of agricultural and food chemistry 23 27808514
2021 MACF1 controls skeletal muscle function through the microtubule-dependent localization of extra-synaptic myonuclei and mitochondria biogenesis. eLife 22 34448452
2012 The neuronal EGF-related gene Nell2 interacts with Macf1 and supports survival of retinal ganglion cells after optic nerve injury. PloS one 21 22496866
2022 A novel circ_MACF1/miR-942-5p/TGFBR2 axis regulates the functional behaviors and drug sensitivity in gefitinib-resistant non-small cell lung cancer cells. BMC pulmonary medicine 18 34996416
2021 MACF1 promotes osteoblast differentiation by sequestering repressors in cytoplasm. Cell death and differentiation 16 33664480
2013 ACF7 regulates colonic permeability. International journal of molecular medicine 16 23426880
2000 Agrobacterium-mediated transformation of the commercially important grapefruit cultivar Rio Red (Citrus paradisi Macf.). Plant cell reports 16 30754857
2012 Ectopic expression of a fruit phytoene synthase from Citrus paradisi Macf. promotes abiotic stress tolerance in transgenic tobacco. Molecular biology reports 15 23011078
2002 Characterization of grapefruit plants (Citrus paradisi Macf.) transformed with citrus tristeza closterovirus genes. Plant cell reports 15 12789444
2019 Microtubule actin crosslinking factor 1 (MACF1) knockdown inhibits RANKL-induced osteoclastogenesis via Akt/GSK3β/NFATc1 signalling pathway. Molecular and cellular endocrinology 14 31260729
2017 Structure of the ACF7 EF-Hand-GAR Module and Delineation of Microtubule Binding Determinants. Structure (London, England : 1993) 14 28602822
2021 MACF1 alleviates aging-related osteoporosis via HES1. Journal of cellular and molecular medicine 12 34133068
2021 MACF1 promotes osteoblastic cell migration by regulating MAP1B through the GSK3beta/TCF7 pathway. Bone 10 34700040
2022 The role of MACF1 on acute myeloid leukemia cell proliferation is involved in Runx2-targeted PI3K/Akt signaling. Molecular and cellular biochemistry 9 35857251
2019 Alteration of scaffold: Possible role of MACF1 in Alzheimer's disease pathogenesis. Medical hypotheses 9 31383338
2023 Role of microtubule actin crosslinking factor 1 (MACF1) in bipolar disorder pathophysiology and potential in lithium therapeutic mechanism. Translational psychiatry 8 37353479
2020 MACF1 promotes preosteoblast migration by mediating focal adhesion turnover through EB1. Biology open 8 32139394
2004 Putative protease inhibitor gene discovery and transcript profiling during fruit development and leaf damage in grapefruit (Citrus paradisi Macf.). Gene 8 14729265
2024 LRRC1 knockdown downregulates MACF1 to inhibit the malignant progression of acute myeloid leukemia by inactivating β-catenin/c-Myc signaling. Journal of molecular histology 7 38165568
2021 Familial Psychosis Associated With a Missense Mutation at MACF1 Gene Combined With the Rare Duplications DUP3p26.3 and DUP16q23.3, Affecting the CNTN6 and CDH13 Genes. Frontiers in genetics 7 33897758
2019 The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasis. Scientific reports 7 31118482
2021 MACF1, Involved in the 1p34.2p34.3 Microdeletion Syndrome, is Essential in Cortical Progenitor Polarity and Brain Integrity. Cellular and molecular neurobiology 6 33871731
2017 MicroRNA targeting microtubule cross-linked protein (MACF1) would suppress the invasion and metastasis of malignant tumor. Medical hypotheses 6 28673583
1989 Somatic hybridization in Citrus: navel orange (C. sinensis Osb.) and grapefruit (C. paradisi Macf.). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 6 24225818
2025 Identification of MACF1 as a causative gene of generalised epilepsy. Journal of medical genetics 5 40350249
2011 Characterization and developmental expression of genes encoding the early carotenoid biosynthetic enzymes in Citrus paradisi Macf. Molecular biology reports 5 21594623
2021 Deubiquitylation and stabilization of Acf7 by ubiquitin carboxylterminal hydrolase 14 (USP14) is critical for NSCLC migration. Journal of biosciences 4 33737492
2023 Circ_MACF1 targets miR-421 to upregulate FMO2 to suppress paclitaxel resistance and malignant cellular behaviors in lung adenocarcinoma. Thoracic cancer 3 37814902
2022 Comprehensive ceRNA network for MACF1 regulates osteoblast proliferation. BMC genomics 3 36207684
2025 A Novel Candidate Gene MACF1 is Associated with Autosomal Dominant Non-syndromic Hearing Loss in an Iranian Family. Archives of Iranian medicine 2 40001331
2024 Concurrent de novo MACF1 mutation and inherited 16p13.11 microduplication in a preterm newborn with hypotonia, joint hyperlaxity and multiple congenital malformations: a case report. BMC pediatrics 2 39152427
2024 A missense mutation in the MACF1 gene in a patient with autism spectrum disorder and epilepsy. Journal of medicine and life 2 39781307
2022 MSI1 Stabilizes MACF1 to Inhibit Apoptosis of MC3T3-E1 Cells Induced by High Glucose and Promote Osteogenic Differentiation Through Wnt/β-Catenin Signaling Pathway. Molecular biotechnology 2 36443618
2022 THADA, SDHAF4, and MACF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes. Genes 2 36672824
2025 A clinical and genotype-phenotype analysis of MACF1 variants. American journal of human genetics 1 40925378
2025 Transcriptional activation of MACF1 by NR2F1 drives WNT-mediated focal adhesion and metastasis in lung adenocarcinoma. European journal of medical research 0 41102854
2024 [Myonuclear domain settings by microtubules and MACF1]. Medecine sciences : M/S 0 39555882
2017 [MACF1 knockdown in glioblastoma multiforme cells increases temozolomide-induced cytotoxicity]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 28951359