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Showing GAP43 — GAP-43 is a alias.

GAP43

Neuromodulin · UniProt P17677

Length
238 aa
Mass
24.8 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GAP-43 (B-50/pp46) is a neuron-specific, intracellular peripheral membrane phosphoprotein that is the dominant component of axonal growth-cone membranes and a central regulator of axon outgrowth, growth-cone dynamics, and presynaptic plasticity (PMID:3738509, PMID:3517863, PMID:3712014, PMID:3249243). It is anchored to the cytoplasmic face of axonal and growth-cone plasma membranes (PMID:2531216) through tandem palmitoylation of two N-terminal cysteines, a short N-terminal signal that is both necessary and sufficient for targeting to growth-cone membranes, filopodia, and detergent-resistant lipid rafts (PMID:2797153, PMID:9774477, PMID:10532807); initial palmitoylation occurs at the ERGIC/Golgi (PMID:10446390) and is dynamically reversed by the thioesterase APT-2 (PMID:21152083). Through its N-terminal domain GAP-43 activates the heterotrimeric G-protein Go and amplifies GPCR signaling, an activity gated off by palmitoylation, while the same peptide drives growth-cone collapse in a pertussis-toxin-sensitive manner (PMID:1534749, PMID:8083750, PMID:7685122). GAP-43 is a major substrate of PKC (and, at a distinct site, casein kinase II) at the growth cone (PMID:3249243, PMID:3178803), and its phosphorylation state couples receptor and depolarization signals to neurotransmitter release and to a calmodulin-sequestering 'sponge' function that buffers Ca2+ signaling (PMID:2562806, PMID:2531215, PMID:1979675). Mechanistically it binds F-actin without altering polymerization (PMID:8377002), drives Rho-GTPase-dependent filopodial extension even in non-neuronal cells (PMID:2658062, PMID:9614174), engages the Ca2+-dependent synaptic core complex and rabaptin-5 to link vesicle fusion and endocytic recycling (PMID:9230128, PMID:9742146), and its phosphorylation enhances presynaptic LTP (PMID:12099903). Its expression is controlled transcriptionally by an axotomy-induced p53-CBP/p300 complex (PMID:19057620) and post-transcriptionally by axonal mRNA stabilization via HuD and NGF-dependent ARPP-19 (PMID:12221279, PMID:15389607), with axonal GAP-43 translation specifically supporting axon elongation (PMID:23426659). Loss-of-function in mice produces axon guidance and arborization defects in retinotectal and serotonergic projections and disrupted neural precursor differentiation (PMID:11978831, PMID:10072298, PMID:15234344).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1986 High

    Established GAP-43 as a developmentally regulated, neuron-specific growth-cone membrane phosphoprotein, defining it as a candidate molecular substrate of axon growth and a PKC target.

    Evidence Subcellular fractionation, immunohistochemistry, metabolic labeling and in vitro kinase assays in developing rat brain

    PMID:3517863 PMID:3712014 PMID:3738509

    Open questions at the time
    • Primary sequence and membrane topology not yet defined
    • Functional consequence of phosphorylation unknown
  2. 1987 High

    Cloning resolved that GAP-43 is a hydrophilic protein lacking transmembrane domains, expressed exclusively in neurons from a single gene regulated largely transcriptionally, explaining its cytoplasmic-face membrane association.

    Evidence cDNA cloning, sequence analysis, Northern blot and in situ hybridization

    PMID:2437653 PMID:3581170

    Open questions at the time
    • Mechanism of membrane anchoring not yet identified
    • No functional domain mapping
  3. 1989 High

    Defined the N-terminal palmitoylated cysteines as the membrane/growth-cone targeting signal and showed GAP-43 alone is sufficient to induce filopodia, establishing a direct role in membrane structure and process extension.

    Evidence Mutational analysis with fusion proteins, confocal imaging, and transfection of non-neuronal cell lines

    PMID:2658062 PMID:2797153

    Open questions at the time
    • Downstream effectors of filopodia induction unknown
    • Link to actin not yet established
  4. 1989 High

    Linked GAP-43 phosphorylation to receptor- and depolarization-driven PKC signaling and neurotransmitter release at growth cones and presynaptic membranes, and localized it ultrastructurally to the cytoplasmic axonal/growth-cone membrane.

    Evidence 32P-labeling, immunoprecipitation, PKC and muscarinic agonist/antagonist pharmacology in hippocampal slices and isolated growth cones, immunoelectron microscopy

    PMID:2531215 PMID:2531216 PMID:2562806 PMID:3249243

    Open questions at the time
    • Molecular target of phosphorylation-dependent regulation unresolved
    • Causal link between phosphorylation and release not direct
  5. 1988 High

    Identified casein kinase II as a second kinase acting on a distinct serine site, showing GAP-43 integrates multiple signaling inputs.

    Evidence In vitro kinase assay, tryptic phosphopeptide mapping and phosphoamino acid analysis

    PMID:3178803

    Open questions at the time
    • Functional role of the CKII site not defined in this study
  6. 1990 Medium

    Defined GAP-43 as a calmodulin 'sponge' and tied it to the actin-rich membrane skeleton and to polarized axonal sorting, connecting Ca2+ buffering to growth-cone cytoskeleton and neuronal polarity.

    Evidence In vitro calmodulin-binding assays, detergent-resistant membrane skeleton fractionation, and immunofluorescence of polarizing hippocampal neurons

    PMID:1979675 PMID:2137528 PMID:2137532

    Open questions at the time
    • In vivo significance of calmodulin sequestration not demonstrated
    • Mechanism of polarized sorting not defined
  7. 1992 High

    Demonstrated that palmitoylation acts as a reversible on/off switch for GAP-43 activation of Go and that GAP-43 binds F-actin without altering its dynamics, separating its signaling and cytoskeletal-scaffolding roles.

    Evidence In vitro G-protein activation assays with defined palmitoylation states and F-actin co-sedimentation/polymerization assays with purified proteins

    PMID:1534749 PMID:8377002

    Open questions at the time
    • Identity of in-cell palmitoylating/depalmitoylating enzymes unknown
    • Functional consequence of F-actin binding undefined
  8. 1992 Medium

    Linked phosphorylation state spatially to growth-cone behavior, showing low phospho-GAP-43 in motile and high in stationary growth cones.

    Evidence Phospho-specific antibody immunofluorescence in cultured DRG neurons

    PMID:1460463

    Open questions at the time
    • Correlative, not causal
    • Single imaging method
  9. 1993 High

    Established GAP-43 as an intracellular amplifier of Go/GPCR signaling and mapped the N-terminal residues required, connecting G-protein activation to growth-cone collapse and neurite outgrowth control.

    Evidence In vitro Go activation assays with peptide mutagenesis, pertussis toxin epistasis, and Xenopus oocyte microinjection electrophysiology

    PMID:7685122 PMID:8083750

    Open questions at the time
    • Endogenous GPCRs coupled to GAP-43 in neurons not identified
    • Integration with PKC signaling unresolved
  10. 1997 Medium

    Placed GAP-43 within the Ca2+-dependent synaptic vesicle fusion machinery by demonstrating Ca2+-regulated interaction with the SNARE core complex and calmodulin.

    Evidence Chemical cross-linking, co-immunoprecipitation and in vitro Ca2+-titrated binding in rat brain and PC12 cells

    PMID:9230128

    Open questions at the time
    • Cross-linking requirement implies low-affinity interaction
    • Direct contribution to fusion not measured
  11. 1998 High

    Refined membrane targeting to tandem-palmitoylated cysteine-dependent lipid raft association and added a rabaptin-5/endocytosis link and a Rho-dependent (not Cdc42/Rac) mechanism for filopodia formation.

    Evidence DRM fractionation with cysteine mutagenesis, yeast two-hybrid and endocytosis assays, and dominant-negative GTPase/C3-transferase epistasis

    PMID:9614174 PMID:9742146 PMID:9774477

    Open questions at the time
    • Link between raft targeting and Rho activation not mechanistically bridged
    • Rabaptin-5 interaction from single lab
  12. 1999 Medium

    Confirmed neuronal raft association in situ and showed GAP-43 is required for retinotectal topographic axon guidance, connecting molecular localization to circuit-level wiring.

    Evidence Immunofluorescence with Thy-1 cross-linking, time-lapse imaging, and axonal tracing in GAP-43 knockout mice

    PMID:10072298 PMID:10532807

    Open questions at the time
    • Mechanistic link between guidance defect and raft/signaling functions not established
  13. 1999 Medium

    Localized the initial palmitoylation step to the ERGIC/Golgi rather than the plasma membrane, defining the biosynthetic route to membrane targeting.

    Evidence In vitro translation, subcellular fractionation, Triton X-114 partitioning with palmitoylation inhibitors

    PMID:10446390

    Open questions at the time
    • Palmitoyl-transferase identity not determined
    • Trafficking from Golgi to growth cone not traced
  14. 2000 Medium

    Revealed an unexpected role in regulating neuronal survival, with GAP-43 loss protecting NGF/BDNF-dependent sensory neurons and Purkinje cells from apoptosis.

    Evidence Apoptosis assays in GAP-43 heterozygous and null neurons under semaphorin III and trophic-factor withdrawal

    PMID:10882480

    Open questions at the time
    • Molecular pathway linking GAP-43 to apoptosis unknown
    • Single lab
  15. 2002 High

    Demonstrated phosphorylation-state-specific control of presynaptic plasticity and a requirement for GAP-43 in serotonergic axon pathfinding and arborization.

    Evidence Phosphomimetic/non-phosphorylatable transgenic and null mice with hippocampal slice electrophysiology and 5-HT immunohistochemistry/stereology

    PMID:11978831 PMID:12099903

    Open questions at the time
    • Presynaptic effector mechanism downstream of phospho-GAP-43 not defined
    • Guidance defect mechanism unresolved
  16. 2002 High

    Identified ARPP-19 as an NGF-dependent 3'UTR-binding stabilizer of GAP-43 mRNA, establishing post-transcriptional control of GAP-43 levels.

    Evidence RNA-binding assays and reporter expression in PC12 cells with PKA-site mutagenesis of ARPP-19

    PMID:12221279

    Open questions at the time
    • Whether ARPP-19 acts in axons in vivo not shown
  17. 2004 High

    Showed HuD stabilizes GAP-43 mRNA within growth cones in an actin-dependent manner and that GAP-43 is required for early multipotent neural precursor and astrocyte differentiation, broadening its role beyond axon growth.

    Evidence HuD knockout mice with mRNA stability assays and localization; GAP-43-null P19 cells and mouse brain with GFAP immunostaining and cell-cycle analysis

    PMID:15234344 PMID:15389607

    Open questions at the time
    • Precursor differentiation mechanism not defined
    • HuD/ARPP-19 relationship not integrated
  18. 2006 Medium

    Placed GAP-43 in an NCAM-180/spectrin signaling complex governing pathway choice in neurite outgrowth, requiring both PKC and CKII phosphorylation.

    Evidence Overexpression, dominant-negative constructs and PKC/CKII inhibition in PC12E2 and hippocampal neurons

    PMID:17212696

    Open questions at the time
    • Direct GAP-43-spectrin contact not demonstrated
    • Single lab
  19. 2008 High

    Identified an axotomy-induced acetylated-p53/CBP-p300 complex as a direct transcriptional driver of GAP-43, linking injury signaling to a regeneration program.

    Evidence ChIP and promoter binding in chromatin context, p53-null mice and in vivo facial nerve axotomy

    PMID:19057620

    Open questions at the time
    • Upstream signal activating p53 acetylation after axotomy not defined
  20. 2009 Medium

    Revealed a non-enzymatic prolyl oligopeptidase interaction modulating growth-cone dynamics, expanding GAP-43's protein-interaction network.

    Evidence PO-null mice with catalytically dead PO rescue and binding assays

    PMID:19332125

    Open questions at the time
    • Functional consequence of the GAP-43-PO interaction not mapped
    • Single lab
  21. 2010 High

    Identified APT-2 as the selective thioesterase that depalmitoylates GAP-43, completing the dynamic palmitoylation cycle controlling its localization.

    Evidence Fluorescent fusion deacylation kinetics and localization with APT-1 negative control in CHO-K1 and HeLa cells

    PMID:21152083

    Open questions at the time
    • Regulation of APT-2 activity on GAP-43 in neurons not shown
  22. 2013 High

    Demonstrated that local axonal translation of GAP-43 mRNA specifically supports axon elongation, distinct from beta-actin's role in branching, mechanistically separating these growth modes.

    Evidence 3'UTR/ZBP1 competition assays, siRNA-resistant axon-restricted rescue, and in ovo electroporation in DRG neurons

    PMID:23426659

    Open questions at the time
    • How locally synthesized GAP-43 protein drives elongation at the molecular level not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GAP-43's distinct molecular activities — Go activation, calmodulin sequestration, F-actin/Rho-dependent filopodia, SNARE/endocytic coupling — are coordinated in space and time within a single growth cone, and which are rate-limiting for axon guidance versus regeneration, remains unresolved.
  • No integrated model linking the multiple effector functions
  • Relative contribution of each activity to in vivo phenotypes unquantified
  • No structural model of GAP-43 in any complex

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-112316 Neuronal System 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
ARPP19CALM (CALMODULIN)ELAVL4 (HUD)LYPLA2 (APT-2)NCAM1PREP (PROLYL OLIGOPEPTIDASE)RABEP1 (RABAPTIN-5)TP53
Complex memberships
NCAM-180/spectrin/GAP-43 complexsynaptic SNARE core complex (syntaxin/SNAP-25/VAMP/synaptotagmin)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 GAP-43 (pp46) is a major component of growth-cone membranes in developing rat brain, approximately 12-fold enriched in growth-cone membranes relative to adult synaptic membranes, and is localized specifically to neuropil areas containing growth cones and immature synaptic terminals by subcellular fractionation and immunohistochemistry. Subcellular fractionation, immunohistochemistry Science High 3517863 3738509
1986 GAP-43 is an acidic, axonally transported membrane protein whose synthesis is elevated 20–100-fold during axon development/regeneration and is regulated largely at the mRNA level; it co-migrates with B-50, a synaptic membrane PKC substrate in adult brain, and is phosphorylated 4–7-fold more in growth-cone membranes than in mature synaptic membranes by endogenous kinases. Metabolic labeling, 2D-PAGE, in vitro kinase assay, cell-free translation The Journal of Neuroscience High 3712014
1987 The primary structure of GAP-43 is extremely hydrophilic with no transmembrane domains and no N-linked glycosylation sites but has a short N-terminal hydrophobic segment, consistent with cytoplasmic-face membrane association; GAP-43 mRNA is expressed exclusively in neurons and developmental/regeneration changes in synthesis are mediated largely at the transcriptional level from a single gene. cDNA cloning, sequence analysis, Northern blot, in situ hybridization Cell High 2437653 3581170
1989 A short N-terminal stretch of GAP-43 is sufficient to direct membrane targeting to growth-cone membranes and filopodia; mutational analysis and confocal imaging of GAP-43/CAT fusion proteins identified this targeting signal, which depends on palmitoylation of N-terminal cysteines. Mutational analysis, fusion protein expression, laser-scanning confocal microscopy Nature High 2797153
1989 GAP-43 expression in non-neuronal cells (COS, NIH 3T3, CHO) induces numerous long filopodial processes, demonstrating that GAP-43 directly promotes filopodial extension and alters cell membrane structure; the transfected protein associates with the membrane as in neurons. Transient and stable transfection, cell morphology analysis Science High 2658062
1989 GAP-43 is a major PKC substrate in sympathetic neuron growth cones; stimulation of PKC causes ~7-fold increase in phosphorylation of a GAP-43-sized protein, and the protein is distributed at higher levels in growth cones than cell bodies, with strictly intracellular localization. Immunofluorescence, PKC stimulation, electrophoresis The Journal of Neuroscience High 3249243
1989 B-50/GAP-43 phosphorylation in intact rat hippocampal slices is enhanced by K+-depolarization and phorbol esters (PKC activators) under conditions that also stimulate neurotransmitter release; PKC inhibitor polymyxin B reduces both depolarization-induced B-50 phosphorylation and neurotransmitter release, linking B-50 phosphorylation to PKC-mediated neurotransmitter release. 32P-labeling, immunoprecipitation in hippocampal slices, PKC inhibition Journal of Neurochemistry High 2562806
1989 B-50/GAP-43 is located at the cytoplasmic side of the plasma membrane of axons and growth cones (not dendrites), as shown by immunogold labeling on cryosections and pre-embedding peroxidase labeling by electron microscopy. Immunoelectron microscopy (immunogold and peroxidase pre-embedding) The Journal of Neuroscience High 2531216
1989 Muscarinic receptor activation (carbachol) stimulates B-50/GAP-43 phosphorylation in isolated nerve growth cones via PKC; the effect is blocked by atropine and is additive with K+-depolarization, demonstrating receptor-mediated PKC activation at growth cones. 32P-labeling, immunoprecipitation in isolated growth cones, pharmacological antagonism The Journal of Neuroscience High 2531215
1990 GAP-43 is tightly bound to the actin-rich detergent-resistant neuronal membrane skeleton in chick neurons; the chick protein (3D5 antigen) is precipitated by anti-rat GAP-43 antisera and is a major PKC phosphorylation target in the membrane skeleton. Detergent extraction, immunoprecipitation, in vitro kinase assay Journal of Neurochemistry Medium 2137528
1990 GAP-43 selectively distributes to the axonal domain during the establishment of neuronal polarity in hippocampal neurons; before morphological polarity, GAP-43 is distributed equally among all processes, but upon axon specification it becomes preferentially concentrated in the axonal growth cone and is absent from dendrites. Immunofluorescence microscopy of cultured hippocampal neurons The Journal of Neuroscience Medium 2137532
1990 GAP-43 acts as a 'calmodulin sponge': it sequesters calmodulin to submembranous regions at resting Ca2+ and releases free calmodulin upon PKC activation (phosphorylation of GAP-43), providing a mechanism by which GAP-43 regulates calmodulin availability and thereby calcium signaling and neurotransmitter release in axon terminals. Biochemical analysis of calmodulin-binding properties and PKC phosphorylation effects (in vitro binding assays) Neuroscience Research Supplement Medium 1979675
1992 Palmitoylation of GAP-43 at its two N-terminal cysteines regulates its activity: monopalmitoylation reduces and dipalmitoylation abolishes GAP-43's ability to stimulate guanine nucleotide exchange by Go, and this block is reversible, identifying a palmitoylation-dependent on/off switch for G-protein activation. In vitro G-protein activation assay, palmitoylation of synthetic peptides and brain-purified GAP-43, biochemical analysis The EMBO Journal High 1534749
1992 GAP-43 binds to actin filaments (F-actin) in a Ca2+-independent manner without affecting actin polymerization kinetics, critical concentration, filament bundling, severing, or capping; both phosphorylated and dephosphorylated B-50 co-sediment with F-actin. Co-sedimentation assay with purified proteins, pyrene-actin polymerization kinetics, light scattering, electron microscopy, [3H]cytochalasin B binding Journal of Neurochemistry High 8377002
1992 PKC phosphorylation of GAP-43 is dynamically regulated in individual growth cones: motile growth cones have very low phosphorylated GAP-43 whereas stationary growth cones have high levels; increased phosphorylation correlates with reduced neurite extension but not translocation speed, and is spatially heterogeneous within the growth cone. Immunofluorescence with phospho-specific GAP-43 antibody in cultured DRG neurons Journal of Neurobiology Medium 1460463
1993 GAP-43 N-terminal peptide (residues 1–10) stimulates Go GTPase activity, requiring Cys3, Cys4, Arg6, and Lys9; this peptide and the Go-activating peptide mastoparan induce growth cone collapse and inhibit neurite extension in a pertussis-toxin-sensitive, G-protein-dependent manner in embryonic chick neurons. In vitro Go activation assay, peptide-mutagenesis, pertussis toxin treatment, neurite outgrowth assay The Journal of Neuroscience High 8083750
1993 GAP-43 microinjected into Xenopus laevis oocytes augments G protein-coupled receptor transduction 10–100-fold and at higher levels triggers calcium-activated chloride channel currents without receptor stimulation, indicating GAP-43 acts as an intracellular amplifier of GPCR signaling. Microinjection into Xenopus oocytes, electrophysiology, IP3 desensitization Proceedings of the National Academy of Sciences High 7685122
1988 Casein kinase II phosphorylates GAP-43/B-50 at serine residue(s) within a single tryptic peptide with apparent Km of 4 µM and Vmax of 13 nmol/min/mg; this phosphorylation is distinct from the PKC site. In vitro kinase assay, tryptic phosphopeptide mapping, phosphoamino acid analysis, inhibitor studies Biochemical and Biophysical Research Communications High 3178803
1997 GAP-43 interacts Ca2+-dependently with syntaxin, SNAP-25, VAMP, synaptotagmin, and calmodulin in rat brain tissue and NGF-differentiated PC12 cells; in vitro interaction with the synaptic core complex peaks at ~100 µM Ca2+ and is coupled with PKC-mediated phosphorylation of GAP-43, suggesting a role in Ca2+-dependent synaptic vesicle fusion. Chemical cross-linking, co-immunoprecipitation, in vitro binding assay with defined Ca2+ concentrations The Biochemical Journal Medium 9230128
1998 GAP-43 association with detergent-resistant membranes (lipid rafts) requires palmitoylation at both Cys3 and Cys4; mutation of either cysteine prevents DRM association, and an N-terminal 20-aa GAP-43 fragment fused to beta-galactosidase targets efficiently to DRMs, establishing tandem palmitoylated cysteines as a raft-targeting signal. Triton X-100 DRM extraction, site-directed mutagenesis, fusion protein expression in PC12 cells The Journal of Biological Chemistry High 9774477
1998 GAP-43 interacts with rabaptin-5 (an effector of Rab5 involved in endocytosis) in a Ca2+-dependent manner and regulates endocytosis and synaptic vesicle recycling in neurons. Yeast two-hybrid, co-immunoprecipitation, endocytosis assays in neuronal cells The Journal of Neuroscience Medium 9742146
1998 B-50/GAP-43-induced filopodia formation in Rat-1 fibroblasts depends on Rho GTPase but not Cdc42 or Rac; dominant-negative Rho or C. botulinum C3-transferase completely blocks B-50-induced filopodia, whereas dominant-negative Cdc42 or Rac does not. The effect requires intact N-terminal cysteines (membrane association) but not the PKC phosphorylation site. Transfection, dominant-negative GTPase co-expression, C3-transferase treatment, morphological analysis Molecular Biology of the Cell High 9614174
1999 B-50/GAP-43 colocalizes with the raft marker Thy-1 in hippocampal neurons; antibody-mediated Thy-1 cross-linking causes redistribution of B-50 to Thy-1-positive membrane patches (excluding syntaxin), confirming raft association of B-50 in neurons. In Rat1 fibroblasts, motile cells concentrate B-50 at the leading edge coinciding with actin polymerization. Immunofluorescence, antibody-mediated cross-linking, time-lapse microscopy Molecular and Cellular Neurosciences Medium 10532807
1999 Initial palmitoylation of GAP-43 occurs at the ER-Golgi intermediate compartment (ERGIC) and Golgi apparatus, not at the plasma membrane; ERGIC-dependent partitioning into Triton X-114 is blocked by palmitoylation inhibitors (DTT, tunicamycin, low temperature) and by iodoacetamide treatment of GAP-43. In vitro translation, subcellular fractionation, Triton X-114 partitioning, palmitoylation inhibitors Biochimica et Biophysica Acta Medium 10446390
2002 ARPP-19 mediates NGF-dependent stabilization of GAP-43 mRNA: in an NGF-dependent manner, ARPP-19 binds to the 3' UTR region of GAP-43 mRNA critical for mRNA half-life regulation; overexpression of wild-type ARPP-19 increases NGF-dependent GAP-43 reporter expression, while mutation of the PKA phosphorylation site Ser104 abolishes this regulation. RNA-binding assay, reporter construct expression in PC12 cells, site-directed mutagenesis of ARPP-19 Proceedings of the National Academy of Sciences High 12221279
2004 The RNA-binding protein HuD colocalizes with GAP-43 mRNA and ribosomes in growth cone central and peripheral domains; HuD granule distribution in growth cones depends on actin filaments but not microtubules; in HuD-KO mice, GAP-43 mRNA is significantly less stable, confirming HuD stabilizes GAP-43 mRNA in growth cones. Immunofluorescence, cytoskeletal drug treatments, HuD knockout mice, mRNA stability assay Journal of Neurobiology High 15389607
2006 GAP-43 potentiates NCAM-180-mediated neurite outgrowth via a functional complex of NCAM-180/spectrin/GAP-43; in the presence of GAP-43, NCAM-180 signaling through spectrin (modulating actin cytoskeleton) predominates, while in its absence NCAM-140/Fyn pathway is dominant. PKC and casein kinase II phosphorylation of GAP-43 are both required for NCAM-induced outgrowth; membrane association of GAP-43 is essential. Overexpression in PC12E2 and hippocampal neurons, pharmacological inhibition of PKC/CKII, dominant-negative constructs, neurite outgrowth assay Journal of Neurochemistry Medium 17212696
2008 A p53-CBP/p300 transcriptional complex directly regulates GAP-43 gene expression: acetylated p53 (K372/373/382) binds specific elements on the GAP-43 promoter in a chromatin context via CBP/p300; this complex is induced by axotomy in facial motor neurons and drives axon outgrowth and regeneration as shown by comparison of wild-type and p53-null mice. Chromatin immunoprecipitation (ChIP), promoter binding assay, p53 knockout mouse model, in vivo axotomy Cell Death and Differentiation High 19057620
2009 Prolyl oligopeptidase (PO) binds to GAP-43 and modulates growth cone dynamics through a non-enzymatic mechanism: PO null mice have altered growth cone dynamics, and re-expression of either native or catalytically dead PO rescues the wild-type phenotype. PO null mouse model, rescue with catalytically dead PO, binding interaction assay Molecular and Cellular Neurosciences Medium 19332125
2010 Acyl-protein thioesterase 2 (APT-2), not APT-1, mediates deacylation of GAP-43: APT-2 overexpression increases deacylation rate of single-acylated GAP-43 mutants and alters steady-state localization of diacylated GAP-43 in both CHO-K1 and HeLa cells; APT-1 overexpression had no effect, and APT-1 is absent from CHO-K1 cells. Fluorescent fusion constructs, live cell imaging, RT-PCR, deacylation kinetics measurement, overexpression in two cell lines PLoS ONE High 21152083
2002 GAP-43 is essential for normal pathfinding and arborization of serotonergic axons from the raphe nuclei: GAP-43-null mice show nearly complete failure of 5-HT axons to innervate cortex and hippocampus, with aberrant innervation of the thalamus, while dorsal raphe neuron numbers are unaffected, demonstrating a specific axon guidance/arborization role. GAP-43 knockout mouse, 5-HT immunohistochemistry, unbiased stereological cell counting, HPLC of neurotransmitters The Journal of Neuroscience High 11978831
1999 GAP-43 is required for proper retinotectal topographic organization: GAP-43-null mice show aberrant ipsilateral optic tract growth, failure to form proper terminal zones in the lateral geniculate nucleus, and intermingled RGC axons in the superior colliculus. Gene knockout (exon 1 disruption), axonal tracing, histological analysis Experimental Neurology High 10072298
2000 Absence of GAP-43 protects specific sensory neurons from apoptosis: GAP-43 (+/-) and null mutant mice show dramatically increased resistance of NGF- and BDNF-dependent (but not NT-3-dependent) sensory neurons to semaphorin III-induced death and trophic factor deprivation-induced apoptosis; early postnatal Purkinje cells from GAP-43 (+/-) mice are also more resistant to death in organotypic culture. GAP-43 heterozygous and null mutant mouse neurons, apoptosis assay, semaphorin III treatment, trophic factor withdrawal Molecular and Cellular Neurosciences Medium 10882480
2002 Constitutively phosphorylated GAP-43 (phosphomimetic transgene) enhances long-term potentiation in CA1 hippocampal slices and increases paired-pulse facilitation and summation during high-frequency bursts, indicating that PKC phosphorylation of GAP-43 regulates presynaptic properties underlying LTP. Non-phosphorylatable GAP-43 or GAP-43-null mice do not show this LTP enhancement. Transgenic mice expressing phosphomimetic or non-phosphorylatable GAP-43, hippocampal slice electrophysiology, comparison with GAP-43-null mice The European Journal of Neuroscience High 12099903
2013 Axonal translation of GAP-43 mRNA supports elongating axon growth while axonal translation of beta-actin mRNA supports branching: competition between GAP-43 and beta-actin 3'UTRs for ZBP1 binding and axonal localization was exploited to show that increasing axonal GAP-43 synthesis produces long unbranched axons, and in vivo electroporation of axonally targeted GAP-43 mRNA increases sensory axon length. 3'UTR competition assay, siRNA knockdown with siRNA-resistant rescue constructs restricted to axonal localization, in ovo electroporation, DRG culture The Journal of Neuroscience High 23426659
2004 Failure to express GAP-43 disrupts an early multipotent neural precursor, inhibiting both neurogenesis and radial glia-derived astrocyte differentiation: in GAP-43 null P19 cells and GAP-43(-/-) cerebellum/telencephalon, radial glia fail to exit the cell cycle and fail to acquire GFAP, while LIF-stimulated non-radial glia astrocytes are less affected. P19 EC cell model (GAP-43 null), GAP-43(-/-) mouse brain tissue, GFAP immunostaining, cell cycle analysis Molecular and Cellular Neurosciences Medium 15234344

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 GAP-43: an intrinsic determinant of neuronal development and plasticity. Trends in neurosciences 1143 9023877
1986 Growth-associated protein, GAP-43, a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to pp46, a major polypeptide of a subcellular fraction enriched in growth cones. Proceedings of the National Academy of Sciences of the United States of America 525 3517863
1986 A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes. Science (New York, N.Y.) 439 3738509
1986 A protein associated with axon growth, GAP-43, is widely distributed and developmentally regulated in rat CNS. The Journal of neuroscience : the official journal of the Society for Neuroscience 410 3712014
1987 Primary structure and transcriptional regulation of GAP-43, a protein associated with nerve growth. Cell 356 3581170
1987 Cloning of complementary DNA for GAP-43, a neuronal growth-related protein. Science (New York, N.Y.) 355 2437653
1989 Expression of growth-associated protein B-50 (GAP43) in dorsal root ganglia and sciatic nerve during regenerative sprouting. The Journal of neuroscience : the official journal of the Society for Neuroscience 218 2552034
1990 Changes in the distribution of GAP-43 during the development of neuronal polarity. The Journal of neuroscience : the official journal of the Society for Neuroscience 215 2137532
1988 Growth-associated protein GAP-43 is expressed selectively in associative regions of the adult human brain. Proceedings of the National Academy of Sciences of the United States of America 215 3368468
1989 The neuronal growth-associated protein GAP-43 induces filopodia in non-neuronal cells. Science (New York, N.Y.) 213 2658062
2006 Molecular mechanisms, biological actions, and neuropharmacology of the growth-associated protein GAP-43. Current neuropharmacology 207 18654638
1989 Phosphorylation of B-50 (GAP43) is correlated with neurotransmitter release in rat hippocampal slices. Journal of neurochemistry 189 2562806
1992 GAP-43 as a plasticity protein in neuronal form and repair. Journal of neurobiology 176 1431834
1991 B-50 (GAP-43): biochemistry and functional neurochemistry of a neuron-specific phosphoprotein. Journal of neurochemistry 169 1848274
1989 A membrane-targeting signal in the amino terminus of the neuronal protein GAP-43. Nature 167 2797153
1994 GAP-43 expression in primary sensory neurons following central axotomy. The Journal of neuroscience : the official journal of the Society for Neuroscience 154 8027785
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