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Showing MACF1 — ACF7 is a alias.

MACF1

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

Length
7388 aa
Mass
838.3 kDa
Annotated
2026-06-10
77 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MACF1/ACF7 is a giant spectraplakin scaffold that physically integrates the actin and microtubule cytoskeletons to drive cell polarization, directional migration, and tissue morphogenesis (PMID:10601340, PMID:14636561). It binds F-actin through an N-terminal calponin-homology actin-binding domain and engages and stabilizes microtubules through a C-terminal module in which a GAR domain and adjacent GSR repeats cooperate to bundle and protect MTs, with structural work resolving an EF1-EF2/GAR unit that coordinates Ca2+ and a Zn2+-binding GAR fold required for MT binding (PMID:11112700, PMID:28602822). Beyond passive crosslinking, ACF7 carries an intrinsic actin-regulated ATPase activity that is indispensable for guiding microtubule plus ends along actin to focal adhesions and enabling directional epidermal migration (PMID:18854161). Its cytoskeletal coupling is dynamically gated by phosphorylation: GSK3β phosphorylates the MT-binding domain to uncouple ACF7 from microtubules, a step relieved by Wnt-mediated GSK3β inhibition, while Src/FAK phosphorylates a tyrosine in the CH domain to control actin binding and focal adhesion dynamics (PMID:21295697, PMID:27216888). ACF7 also participates directly in Wnt signaling by escorting the Axin/β-catenin/GSK3β/APC complex to LRP6 at the membrane to promote β-catenin-dependent transcription (PMID:16815997), and anchors noncentrosomal microtubule minus ends through CAMSAP3 to establish epithelial apical-basal polarity (PMID:27802168, PMID:27693509). Through these activities it organizes the cytoskeleton at the neuromuscular junction by binding Rapsyn and clustering EB1, MAP1b, and Vinculin (PMID:30842214), positions myonuclei and shapes the perinuclear MT network in skeletal muscle (PMID:34448452), and is required for basal body docking and ciliogenesis (PMID:27783952). ACF7 protein levels are set by an opposing E3 ligase HectD1 (degradation) and deubiquitinase USP14 (stabilization), tuning its pro-migratory and EMT-promoting output (PMID:29386124, PMID:33737492). De novo missense variants in the GAR and EF-hand microtubule-binding module cause a distinctive lissencephaly with brainstem malformation, with variant proteins showing increased microtubule binding consistent with a toxic gain-of-function mechanism (PMID:30471716, PMID:40925378).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1999 High

    Established the foundational identity of MACF1 as a bona fide cytoskeletal crosslinker by showing it physically engages both actin and microtubules through separate terminal domains.

    Evidence In vitro binding assays and domain-construct transfection with immunofluorescence

    PMID:10601340

    Open questions at the time
    • Did not resolve which C-terminal subdomains mediate MT binding versus stabilization
    • No in vivo functional consequence established
  2. 2001 High

    Dissected the C-terminal MT-binding apparatus, distinguishing a GAR domain that binds/stabilizes MTs from a GSR-repeat domain that bundles them, defining how MACF1 stabilizes the MT network.

    Evidence Domain dissection with in vitro MT-binding and nocodazole-resistance assays in transfected cells

    PMID:11112700

    Open questions at the time
    • Atomic-resolution structure of these domains not yet determined
    • Regulation of these binding activities unaddressed
  3. 2003 High

    Showed via genetic null and domain rescue that MACF1 is required to guide MT growth along actin and tether MTs at cortical sites, establishing it as an essential integrator of MT-actin dynamics for polarized migration.

    Evidence ACF7-null endodermal cells, live imaging, domain-specific rescue

    PMID:14636561

    Open questions at the time
    • Did not explain the energetic/enzymatic basis of MT guidance
    • Upstream regulators of cortical tethering unknown
  4. 2004 Medium

    Linked MACF1 to membrane trafficking by identifying a direct interaction with the Golgi protein p230/Golgin-245 required for GPI-anchored cargo transport from the TGN.

    Evidence Yeast two-hybrid, Co-IP, in vitro binding, dominant-negative interference in HeLa cells

    PMID:15265687

    Open questions at the time
    • Single lab, no in vivo confirmation
    • Mechanistic link between cytoskeletal crosslinking and cargo selectivity unresolved
  5. 2006 High

    Placed MACF1 in the Wnt pathway as a factor that escorts the Axin/β-catenin/GSK3β/APC complex to LRP6, connecting cytoskeletal scaffolding to canonical Wnt transcriptional output.

    Evidence Reciprocal Co-IP, siRNA knockdown, luciferase reporter, knockout mice phenocopying Wnt-3/LRP5/6 mutants

    PMID:16815997

    Open questions at the time
    • Direct binding partner within the Axin complex not pinpointed
    • Whether cytoskeletal binding is needed for complex translocation unresolved
  6. 2007 High

    Defined a direct neuromuscular interaction by mapping ACF7's actin-binding domain to the TPR domains of rapsyn, implicating MACF1 in synaptic scaffold organization.

    Evidence Co-IP, surface plasmon resonance, blot overlay, co-expression in fibroblasts

    PMID:17222516

    Open questions at the time
    • Functional consequence at the NMJ not yet tested in this study
    • Stoichiometry and regulation of the interaction unknown
  7. 2008 High

    Revealed that MACF1 is an active enzyme, not merely a passive crosslinker: an intrinsic actin-regulated ATPase is indispensable for targeting MTs to focal adhesions and directional epidermal migration.

    Evidence Conditional epidermal KO, ATPase activity assays, domain rescue, live imaging

    PMID:18854161

    Open questions at the time
    • Mechanistic coupling of ATP hydrolysis to MT movement not structurally resolved
    • Regulators of the ATPase cycle unidentified
  8. 2009 Medium

    Extended MACF1 function to neuronal MT organization and identified a filopodia-formation mechanism via EF-hand motifs and the translational regulator eIF5C, separating MT-organizing from filopodial roles.

    Evidence Neuronal knockdown/overexpression, domain deletion, Co-IP with eIF5C (Drosophila Shot ortholog)

    PMID:19571116

    Open questions at the time
    • Single lab
    • Mechanism by which a translational regulator couples to MACF1 unclear
  9. 2010 Medium

    Identified an ATPase-independent membrane-recruitment route in which ErbB2-Memo-mDia1 signaling inhibits GSK3 to localize ACF7 to the membrane for MT capture during migration.

    Evidence RNAi, live-cell imaging, overexpression rescue, epistasis

    PMID:20937854

    Open questions at the time
    • Single lab
    • Direct membrane anchor for ACF7 in this context not defined
  10. 2011 High

    Pinpointed GSK3β phosphorylation of ACF7's MT-binding domain as the switch that uncouples ACF7 from MTs, establishing dynamic phosphocycling as essential for directed stem-cell migration downstream of Wnt.

    Evidence In vitro kinase assay, phospho-site mutagenesis, phospho-mimetic/refractory rescue in ACF7-null skin, live imaging

    PMID:21295697

    Open questions at the time
    • Phosphatase that reverses the modification unidentified
    • Spatial control of phosphorylation during migration not mapped
  11. 2012 Medium

    Defined an ELMO-ACF7 interaction (ELMO polyproline to ACF7 last spectrin repeat) that recruits ACF7 to the membrane for MT capture and protrusion persistence, requiring the Rac-GEF DOCK180.

    Evidence Co-IP, domain mapping, live-cell protrusion and MT imaging

    PMID:23184944

    Open questions at the time
    • Single lab
    • Interplay with the ErbB2-Memo recruitment route not reconciled
  12. 2014 Medium

    Showed MACF1 controls cortical pyramidal neuron migration via MT dynamics and physical interaction with GSK-3, extending its migratory scaffold role to brain development.

    Evidence Conditional KO (in utero electroporation), Co-IP, live imaging, MT stability assays

    PMID:25224226

    Open questions at the time
    • Single lab
    • Direct phosphorylation events in neurons not delineated
  13. 2016 High

    Identified the Src/FAK-phosphorylated CH-domain tyrosine, supported by a crystal structure of the N-terminal domain, as essential for ACF7 actin binding and focal adhesion dynamics, adding a second phospho-regulatory axis distinct from GSK3β.

    Evidence Crystal structure, phospho-site mutagenesis, conditional KO mice, in vitro kinase assay

    PMID:27216888

    Open questions at the time
    • How CH-domain and MT-domain phospho-switches are coordinated in time unresolved
    • Phosphatase counterpart unknown
  14. 2016 Medium

    Established that ACF7 anchors noncentrosomal MT minus ends by binding CAMSAP3, coordinating MT-actin crosstalk via retrograde flow to set epithelial polarity, MT orientation, and focal adhesion size.

    Evidence Reciprocal Co-IP, KO cell lines, 3D cyst assays, live imaging, focal adhesion analysis

    PMID:27693509 PMID:27802168

    Open questions at the time
    • Whether minus-end anchoring uses the same domains as plus-end guidance unresolved
    • Single lab for the mechanistic detail
  15. 2016 Medium

    Demonstrated MACF1 is required for ciliogenesis, mediating basal body docking and apical migration with interactions to MKKS and TALPID3, linking the scaffold to ciliary polarity.

    Evidence Conditional KO mice, Co-IP, electron microscopy, immunofluorescence

    PMID:27783952

    Open questions at the time
    • Single lab
    • Direct binding interfaces with ciliary proteins not mapped
  16. 2017 High

    Resolved the atomic structure of the EF1-EF2-GAR MT-binding module, revealing Ca2+- and Zn2+-coordinating folds and a conserved basic patch as the MT-binding determinant, providing the structural basis for MT engagement.

    Evidence X-ray crystallography at 2.8 Å with mutagenesis of MT-binding residues

    PMID:28602822

    Open questions at the time
    • Structure of the full-length protein and actin-binding module in complex not solved
    • How phosphorylation alters the structure not captured
  17. 2017 Medium

    Extended the neuronal migration role to GABAergic interneurons, showing MACF1 controls MT stability and leading process dynamics during cortical interneuron positioning.

    Evidence Conditional KO mice (Dlx5/6-Cre, Nkx2.1-Cre), live imaging, MT stability assays

    PMID:27756764

    Open questions at the time
    • Single lab
    • Molecular partners specific to interneurons not identified
  18. 2017 High

    Showed in zebrafish oocytes that Macf1a links cortical actin (not MTs) to the Balbiani Body for granule dissociation and nuclear positioning, revealing an actin-dependent, MT-independent function.

    Evidence CRISPR domain-specific deletion, live imaging, actin/MT depolymerization, localization

    PMID:28880872

    Open questions at the time
    • Direct Balbiani Body binding partner unidentified
    • Conservation of this role in mammals untested in this study
  19. 2018 Medium

    Identified HectD1 as the E3 ligase that targets ACF7 for proteasomal degradation, establishing ubiquitin-mediated control of ACF7 levels as a brake on EMT and metastasis.

    Evidence shRNA screens, Co-IP, ubiquitin assays, mouse metastasis models

    PMID:29386124

    Open questions at the time
    • Single lab
    • Ubiquitination sites on ACF7 not mapped
  20. 2018 Medium

    Linked MACF1 to human disease, showing de novo GAR-domain zinc-binding variants cause lissencephaly with brainstem malformation and short cilia, tying the structurally defined MT-binding module to ciliogenesis defects.

    Evidence Whole-exome/genome sequencing, ciliogenesis assay in patient cells

    PMID:30471716

    Open questions at the time
    • Single study
    • Whether variants act by loss or gain of function not resolved here
  21. 2019 High

    Showed MACF1 concentrates at neuromuscular synapses, binds Rapsyn, and organizes EB1, MAP1b, and Vinculin to support synaptic differentiation and transmission, defining its synaptic cytoskeletal scaffold role in vivo.

    Evidence AChR co-purification, proteomic screen, conditional KO mice, electrophysiology

    PMID:30842214

    Open questions at the time
    • Hierarchy of recruitment among the synaptic partners unresolved
    • Phospho-regulation at the synapse not addressed
  22. 2019 Medium

    Expanded MACF1 into bone biology, showing it acts upstream of Akt/GSK3β/NFATc1 in osteoclastogenesis and of BMP2/Smad/Runx2 in osteoblast differentiation.

    Evidence shRNA knockdown, conditional KO mice, micro-CT, pharmacological rescue, western blot

    PMID:31260729 PMID:31709715

    Open questions at the time
    • Single lab per finding
    • Direct molecular substrate of MACF1 in these pathways not defined
  23. 2020 Medium

    Identified a direct MACF1-SMAD7 interaction promoting SMAD7 nuclear translocation to activate osteogenic programs, adding a cytoplasm-to-nucleus shuttling role in mesenchymal stem cells.

    Evidence Co-IP, nuclear-cytoplasmic fractionation, conditional KO mice

    PMID:32143362

    Open questions at the time
    • Single lab
    • How a cytoskeletal scaffold drives nuclear import mechanistically unclear
  24. 2021 High

    Established MACF1 as essential for myonuclei positioning, perinuclear MT organization, and NMJ integrity in skeletal muscle, conserved from Drosophila to mouse.

    Evidence Conditional KO mice, Drosophila genetics, myotube knockdown, live imaging, EM

    PMID:34448452

    Open questions at the time
    • Link between MACF1 loss and increased mitochondrial biogenesis unexplained
    • Direct nuclear-anchoring partners not identified
  25. 2021 Medium

    Revealed a transcriptional-control mechanism in which MACF1 sequesters repressors (CDK12, MEAF6, TCF12, E2F6) in the cytoplasm and oppositely regulates TCF12/TCF7 localization to promote osteoblast differentiation.

    Evidence Co-IP, nuclear-cytoplasmic fractionation, transcriptomics, knockdown

    PMID:33664480

    Open questions at the time
    • Single lab
    • Concentration-dependent sequestration mechanism not biochemically defined
  26. 2021 Medium

    Detailed how MACF1 promotes osteoblast migration via MAP1B: inhibiting GSK3β to reduce MAP1B-T1265 phosphorylation and strengthening TCF7 occupancy at the Map1b promoter to raise its transcription.

    Evidence siRNA, ChIP-PCR, luciferase reporter, pharmacological epistasis, migration assays

    PMID:34700040

    Open questions at the time
    • Single lab
    • Whether MACF1 directly regulates TCF7 occupancy or acts indirectly unresolved
  27. 2021 Medium

    Identified USP14 as the deubiquitinase that stabilizes ACF7, defining the opposing arm to HectD1 in setting ACF7 protein levels and supporting cancer cell migration.

    Evidence Proteomics, Co-IP, ubiquitination assays, knockdown/overexpression, migration assays

    PMID:33737492

    Open questions at the time
    • Single lab
    • Coordination between USP14 and HectD1 on ACF7 not directly tested
  28. 2025 Medium

    Refined the disease mechanism by showing EF-hand/GAR variants increase microtubule binding (toxic gain-of-function) and that region-specific MACF1 isoforms with distinct exon-1 start sites explain differential cortical phenotypes.

    Evidence MT-binding assays with variant proteins, RNA sequencing, ChIP of human fetal brain

    PMID:40925378

    Open questions at the time
    • Single study
    • Cellular consequence of increased MT binding in neurons not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MACF1's two phospho-switches (GSK3β on the MT domain, Src/FAK on the CH domain), its ATPase cycle, ubiquitin turnover, and its many context-specific partners are integrated within a single giant molecule to produce distinct outputs across tissues remains unresolved.
  • No full-length structure linking actin- and MT-binding modules
  • Phosphatases reversing the regulatory phosphorylations unidentified
  • Mechanistic basis for tissue-specific output selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 4 GO:0005198 structural molecule activity 3 GO:0140657 ATP-dependent activity 1
Localization
GO:0005815 microtubule organizing center 3 GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005929 cilium 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-5653656 Vesicle-mediated transport 1
Partners
AXIN1CAMSAP3ELMOGSK3BHECTD1RAPSNSMAD7USP14
Complex memberships
Axin/β-catenin/GSK3β/APC destruction complexneuromuscular junction synaptic scaffold

Evidence

Reading pass · 31 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; full-length MACF1 associates with both actin and microtubules in transfected cells, establishing it as a microtubule-actin cross-linking factor. In vitro binding assays, transient transfection, immunofluorescence The Journal of cell biology High 10601340
2001 The C-terminus of MACF1 contains at least two microtubule-binding regions: a GAR domain (which binds and partially stabilizes MTs) and a GSR-repeat domain (which bundles MTs); together they synergize to bundle and stabilize MTs against nocodazole. The plakin domain M1 region does not bind MTs in the context of surrounding sequences. Transient transfection, in vitro MT-binding assays, nocodazole resistance assays Journal of cell science High 11112700
2003 ACF7/MACF1 is required for microtubules to grow along polarized actin bundles and pause/tether at actin-rich cortical sites; in ACF7-null endodermal cells, microtubules still bind EB1 and CLIP170 but show altered dynamic instability and skewed trajectories. Rescue requires both ACF7's actin- and microtubule-binding domains, establishing ACF7 as an essential integrator of MT-actin dynamics for cellular polarization and coordinated migration. ACF7 null cell lines, live imaging, domain rescue experiments Cell High 14636561
2006 MACF1 participates in the Wnt signaling pathway: in the absence of Wnt, MACF1 associates with an Axin/β-catenin/GSK3β/APC complex. Upon Wnt stimulation, MACF1 facilitates translocation of the Axin complex to LRP6 at the cell membrane. siRNA knockdown of MACF1 decreases nuclear β-catenin and inhibits TCF/β-catenin-dependent transcriptional activation. MACF1-null embryos phenocopy Wnt-3 and LRP5/6 double-knockout embryos (primitive streak/mesoderm defects). Co-immunoprecipitation, siRNA knockdown, luciferase reporter assay, dominant-negative constructs, MACF1 knockout mice Genes & development High 16815997
2007 The actin-binding domain (N-terminal ABD) of ACF7/MACF1 directly binds to the tetratricopeptide repeat (TPR) domains of rapsyn, as demonstrated by co-expression in fibroblasts, co-immunoprecipitation, surface plasmon resonance, and blot overlay assays. Co-immunoprecipitation, surface plasmon resonance, blot overlay, co-expression in fibroblasts Neuroscience High 17222516
2008 ACF7 harbors an intrinsic actin-regulated ATPase domain that is both functional and essential for targeting microtubules to focal adhesions (FAs), stabilizing FA-actin networks, and enabling directional epidermal cell migration. Binding domains for F-actin, MTs, and MT plus-end proteins alone are insufficient for these functions; the ATPase activity is indispensable. Conditional ACF7 knockout in skin epidermis, ATPase activity assays, domain rescue experiments, live imaging Cell High 18854161
2009 ACF7 (and its Drosophila orthologue Shot) regulates neuronal microtubule organisation (requiring both F-actin and MT-binding domains) and controls filopodia formation through a distinct mechanism requiring EF-hand motifs and interaction with the translational regulator Krasavietz/eIF5C. Neuronal culture knockdown/overexpression, domain deletion analysis, co-immunoprecipitation with eIF5C Journal of cell science Medium 19571116
2010 ErbB2-Memo-mDia1 signaling inhibits GSK3, allowing ACF7 to localize to the plasma membrane and ruffles in a Memo-, GSK3-, and APC-dependent manner; ACF7 at the membrane is both required and sufficient for microtubule capture downstream of ErbB2 in migrating cells. This function does not require ACF7's ATPase activity. RNAi knockdown, live-cell imaging, overexpression rescue, epistasis analysis Proceedings of the National Academy of Sciences of the United States of America Medium 20937854
2011 GSK3β directly phosphorylates ACF7 at sites within its microtubule-binding domain, and this phosphorylation uncouples ACF7 from microtubules. Wnt signaling (which inhibits GSK3β) promotes ACF7–MT coupling. Phosphorylation-refractory ACF7 rescues microtubule architecture but not polarized movement; phosphorylation must be dynamically regulated for directed stem-cell migration during wound repair. In vitro kinase assay, phospho-site mutagenesis, phospho-mimetic and -refractory ACF7 rescue in ACF7-null skin, live imaging of hair follicle stem cells Cell High 21295697
2012 ELMO proteins interact directly with ACF7 via a C-terminal polyproline segment in ELMO and the last spectrin repeat of ACF7. This ELMO–ACF7 interaction recruits ACF7 to the membrane to promote microtubule capture and stability, protrusion persistence, and requires the Rac-GEF DOCK180. Co-immunoprecipitation, domain mapping, live-cell protrusion assays, microtubule imaging The Journal of biological chemistry Medium 23184944
2004 MACF1 C-terminal domain interacts with the N-terminal domain of the Golgi protein p230/Golgin-245, confirmed by yeast two-hybrid, co-immunoprecipitation, and in vitro binding. Expression of dominant-interfering fragments of either protein disrupts transport of a GPI-anchored protein from the TGN to the cell periphery without affecting transmembrane cargo trafficking. Yeast two-hybrid, co-immunoprecipitation, in vitro binding, dominant-negative interference in HeLa cells Experimental cell research Medium 15265687
2014 MACF1 regulates microtubule dynamics and mediates GSK-3 signaling in developing cortical pyramidal neurons; conditional MACF1 deletion disrupts leading-process/centrosome dynamics and neuronal positioning. MACF1 physically interacts with GSK-3 in neurons. Conditional knockout mice (in utero electroporation), co-immunoprecipitation, live imaging, microtubule stability assays Developmental biology Medium 25224226
2016 Src/FAK complex phosphorylates a key tyrosine residue in ACF7's calponin homology (CH) domain, which is essential for F-actin binding of ACF7, focal adhesion dynamics, and epidermal migration in vivo. Crystal structure of ACF7's N-terminal domain was resolved at sufficient resolution to identify the tyrosine residue. Crystal structure determination, phospho-site mutagenesis, conditional knockout mice, in vitro kinase assay Nature communications High 27216888
2016 ACF7/MACF1 specifically binds CAMSAP3 (Nezha) at minus ends of noncentrosomal microtubules and is required for apical localization of CAMSAP3-decorated MT minus ends in intestinal epithelial cells. Loss of ACF7 disrupts polarized epithelial cyst formation in 3D culture. Co-immunoprecipitation, knockout cell lines, 3D epithelial cyst assays, immunofluorescence Journal of cell science Medium 27802168
2016 ACF7/MACF1 (at microtubule minus ends via CAMSAP3 interaction) coordinates noncentrosomal microtubule–actin crosstalk through retrograde flow to maintain MT orientation perpendicular to the cell edge and regulate focal adhesion size and cell migration in Caco2 cells. Co-immunoprecipitation, siRNA knockdown, live imaging, focal adhesion analysis Developmental cell Medium 27693509
2016 MACF1 ablation in the developing retina abolishes ciliogenesis: basal bodies fail to dock to ciliary vesicles or migrate apically, randomizing photoreceptor polarity. MACF1 interacts with ciliary proteins MKKS and TALPID3. Conditional knockout mice, co-immunoprecipitation, electron microscopy, immunofluorescence Cell reports Medium 27783952
2017 Crystal structure of the hACF7 EF1-EF2-GAR microtubule-binding module resolved at 2.8 Å: the EF1-EF2 domain is an EFβ-scaffold with two Ca2+ ions; the GAR domain has a unique α/β sandwich fold coordinating Zn2+. A conserved basic patch distal to the Zn2+-binding site mediates MT binding; EF1-EF2 alone is insufficient for MT binding. X-ray crystallography (2.8 Å), mutagenesis of MT-binding residues, MT-binding assays Structure (London, England : 1993) High 28602822
2017 MACF1 regulates GABAergic interneuron migration and positioning in the developing brain by controlling microtubule stability and leading process dynamics; conditional deletion reduces interneuron speed, alters migration mode, and shortens leading processes and dendrites. Conditional knockout mice (Dlx5/6-Cre, Nkx2.1-Cre), live imaging, microtubule stability assays Cerebral cortex Medium 27756764
2017 In zebrafish oocytes, Macf1a localizes to the Balbiani Body and functions via its actin-binding domain (ABD) to mediate Balbiani Body granule dissociation and nuclear positioning; the plectin repeat domain is dispensable. Disruption of actin (not MTs) phenocopies the macf1a mutant, indicating MACF1 links cortical actin to the Balbiani Body structure. CRISPR/Cas9 domain-specific deletion, live imaging, actin/MT depolymerization, localization studies PLoS genetics High 28880872
2018 The E3 ubiquitin ligase HectD1 promotes ACF7/MACF1 proteasome-mediated degradation. Depletion of HectD1 stabilizes ACF7 protein levels. ACF7 is required for maintenance of the EMT program and migration; HectD1-mediated degradation of ACF7 suppresses EMT and metastasis. shRNA screens, co-immunoprecipitation, ubiquitin assays, mouse metastasis models Cell reports Medium 29386124
2018 De novo missense variants in the zinc-binding residues of MACF1's GAR domain cause a distinctive lissencephaly with brainstem malformation (absent anterior commissure, W-shaped brainstem). Cells from affected individuals show a higher proportion with short cilia, linking GAR domain integrity to ciliogenesis. Whole-exome/genome sequencing, ciliogenesis assay in patient cells American journal of human genetics Medium 30471716
2019 MACF1 is concentrated at neuromuscular synapses where it binds Rapsyn (confirmed by co-purification and interaction assays) and organizes MT-associated proteins EB1 and MAP1b and the actin-associated protein Vinculin at the synapse. MACF1 deficiency impairs synaptic differentiation and neuromuscular transmission. Biochemical co-purification (AChR pull-down), proteomic screen, conditional knockout mice, electrophysiology The Journal of cell biology High 30842214
2019 MACF1 knockdown in osteoclast precursors inhibits RANKL-induced osteoclastogenesis by attenuating phosphorylation of Akt and GSK3β, thereby inhibiting NFATc1 expression. An Akt activator rescues the inhibition, placing MACF1 upstream of Akt/GSK3β/NFATc1 in the osteoclast differentiation pathway. MACF1 knockdown also disrupts actin ring formation. shRNA lentiviral knockdown, western blot, pharmacological rescue with Akt activator, pit resorption assay Molecular and cellular endocrinology Medium 31260729
2019 MACF1 deficiency in osteoblast-specific conditional knockout mice (Osx-Cre) reduces bone mass and impairs osteoblast differentiation. Mechanistically, loss of MACF1 attenuates BMP2/Smad/Runx2 signaling in primary osteoblasts. Conditional knockout mice, micro-CT, primary osteoblast differentiation assays, western blot for Smad/Runx2 signaling Journal of cellular and molecular medicine Medium 31709715
2020 MACF1 directly interacts with SMAD7 and facilitates SMAD7 nuclear translocation, thereby activating downstream osteogenic pathways and promoting bone formation in mesenchymal stem cells. Co-immunoprecipitation, nuclear-cytoplasmic fractionation, conditional knockout mice Cells Medium 32143362
2020 MACF1 promotes preosteoblast migration by mediating EB1 distribution on microtubules, reducing EB1 at focal adhesions, enhancing EB1 co-localization with activated Src, and diminishing EB1-APC co-localization, collectively driving focal adhesion turnover. MACF1 knockdown/overexpression in MC3T3-E1, immunofluorescence co-localization, migration assays Biology open Low 32139394
2021 MACF1 is an essential regulator of myonuclei positioning in skeletal muscle; conditional muscle-specific MACF1 knockout causes aberrant extra-synaptic myonuclei positioning, altered microtubule network organization around nuclei, and NMJ fragmentation. In vitro, MACF1 controls MT dynamics, contributes to MT stabilization during myofiber maturation, and regulates MT density around myonuclei. MACF1 deficiency also leads to increased mitochondria biogenesis. Conditional knockout mice, Drosophila muscle genetics, cultured myotube KD, live imaging, electron microscopy eLife High 34448452
2021 MACF1 promotes osteoblast differentiation by sequestering transcriptional repressors CDK12, MEAF6, TCF12, and E2F6 in the cytoplasm in a concentration-dependent manner, preventing their nuclear activity. MACF1 oppositely regulates TCF12 (repressor) and TCF7 (activator) localization. Co-immunoprecipitation, nuclear-cytoplasmic fractionation, transcriptomic analysis, MACF1 knockdown Cell death and differentiation Medium 33664480
2021 MACF1 promotes osteoblastic cell migration through MAP1B: MACF1 decreases phosphorylation of MAP1B-T1265 by inhibiting GSK3β activity, and upregulates total MAP1B mRNA by strengthening TCF7 binding to the Map1b promoter (confirmed by ChIP-PCR and luciferase assay). siRNA knockdown, ChIP-PCR, luciferase reporter assay, LiCl/Wortmannin pharmacological epistasis, wound healing and transwell assays Bone Medium 34700040
2021 USP14 is identified as a deubiquitinase for ACF7/MACF1: USP14 physically interacts with ACF7 and stabilizes ACF7 protein levels by inhibiting its ubiquitin-proteasome-dependent degradation. USP14 knockdown reduces ACF7 levels and inhibits NSCLC cell migration. Proteomic approach, co-immunoprecipitation, overexpression/knockdown, ubiquitination assay, migration assay Journal of biosciences Medium 33737492
2025 Variants in the EF-hand domains of MACF1 (outside the GAR domain) result in brain malformation; experimental evidence shows that EF-hand/GAR module variants increase microtubule binding, suggesting a toxic gain-of-function mechanism. RNA sequencing and ChIP analyses of human fetal brain reveal five MACF1 isoforms with region-specific expression differing in exon 1 transcription start sites, explaining differential cortical phenotypes. Microtubule-binding assay with variant proteins, RNA sequencing, ChIP analysis of human fetal brain American journal of human genetics Medium 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 156 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 71 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
2017 The role of MACF1 in nervous system development and maintenance. Seminars in cell & developmental biology 40 28579452
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
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 38 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 25 33816492
2020 Mesenchymal MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation. Cells 25 32143362
2016 Genetic Variants of Microtubule Actin Cross-linking Factor 1 (MACF1) Confer Risk for Parkinson's Disease. Molecular neurobiology 24 27021023
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 24 27808514
2018 MACF1 Overexpression by Transfecting the 21 kbp Large Plasmid PEGFP-C1A-ACF7 Promotes Osteoblast Differentiation and Bone Formation. Human gene therapy 23 29334773
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 22 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
2012 Ectopic expression of a fruit phytoene synthase from Citrus paradisi Macf. promotes abiotic stress tolerance in transgenic tobacco. Molecular biology reports 16 23011078
2000 Agrobacterium-mediated transformation of the commercially important grapefruit cultivar Rio Red (Citrus paradisi Macf.). Plant cell reports 16 30754857
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 13 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
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 8 33897758
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
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

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