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.

Meiri, Karina F.; Pfenninger, Karl H.; Willard, Mark

doi:10.1073/pnas.83.10.3537

Cited by 438 publications

(265 citation statements)

References 21 publications

Supporting

Mentioning

251

Contrasting

Unclassified

Order By: Relevance

“…4A). To confirm this observation, we examined the level of GAP43 in the culture, which serves as the marker of neurite outgrowth 23, and found that GAP43 protein was apparently increased in the NSC‐derived neuron culture by morin hydrate treatment (Fig. 4B).…”

Section: Resultsmentioning

confidence: 71%

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

Jia

Zhang

et al. 2016

J Cellular Molecular Medi

View full text Add to dashboard Cite

We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs) isolated from mouse inner ear and its potential in protecting neuronal hearing loss. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays were employed to assess the effect of morin hydrate on the viability and proliferation of in vitro NSC culture. The NSCs were then differentiated into neurons, in which neurosphere formation and differentiation were evaluated, followed by neurite outgrowth and neural excitability measurements in the subsequent in vitro neuronal network. Mechanotransduction of cochlea ex vivo culture and auditory brainstem responses threshold and distortion product optoacoustic emissions amplitude in mouse ototoxicity model were also measured following gentamicin treatment to investigate the protective role of morin hydrate against neuronal hearing loss. Morin hydrate improved viability and proliferation, neurosphere formation and neuronal differentiation of inner ear NSCs, and promoted in vitro neuronal network functions. In both ex vivo and in vivo ototoxicity models, morin hydrate prevented gentamicin‐induced neuronal hearing loss. Morin hydrate exhibited potent properties in promoting growth and differentiation of inner ear NSCs into functional neurons and protecting from gentamicin ototoxicity. Our study supports its clinical potential in treating neuronal hearing loss.

show abstract

Section: Resultsmentioning

confidence: 71%

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

Jia

Zhang

et al. 2016

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Developmentally, RGCs express this protein during axon outgrowth and synaptic refinement, then downregulate it as their connections mature (Skene and Willard, 1981b;Meiri et al, 1986;Moya et al, 1988). Normally, GAP-43 is transiently upregulated after axotomy and declines as RGCs undergo atrophic changes (Doster et al, 1991;Fournier et al, 1997;Wodarczyk et al, 1997;Wouters et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Because RGCs only express GAP-43 during axon outgrowth, probes for this protein enable one to visualize RGCs in a growth state (Meiri et al, 1986;Moya et al, 1988;Doster et al, 1991;Schaden et al, 1994;Berry et al, 1996). In animals having a nerve crush combined with lens puncture, numerous GAP-43-positive axons grew past the injury into the distal optic nerve (Fig.…”

Section: Axon Outgrowthmentioning

confidence: 99%

Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve

et al. 2000

View full text Add to dashboard Cite

In mature mammals, retinal ganglion cells (RGCs) are unable to regenerate their axons after optic nerve injury, and they soon undergo apoptotic cell death. However, a small puncture wound to the lens enhances RGC survival and enables these cells to regenerate their axons into the normally inhibitory environment of the optic nerve. Even when the optic nerve is intact, lens injury stimulates macrophage infiltration into the eye, Mü ller cell activation, and increased GAP-43 expression in ganglion cells across the entire retina. In contrast, axotomy, either alone or combined with intraocular injections that do not infringe on the lens, causes only a minimal change in GAP-43 expression in RGCs and a minimal activation of the other cell types. Combining nerve injury with lens puncture leads to an eightfold increase in RGC survival and a 100-fold increase in the number of axons regenerating beyond the crush site. Macrophage activation appears to play a key role, because intraocular injections of Zymosan, a yeast cell wall preparation, stimulated monocytes in the absence of lens injury and induced RGCs to regenerate their axons into the distal optic nerve.

show abstract

“…We next analyzed the morphology of axon terminals of olfactory neurons during synaptogenesis using GAP43-EGFP as a marker, because GAP43 is enriched in the plasma membrane of axonal growth cones (Meiri et al, 1986;Skene, 1989), and GAP43-EGFP fusion protein was targeted to the growth cone (Nakata et al, 1998). We injected the omp promoter-driven GAP43-EGFP construct (Fig.…”

Section: Axon Terminal Morphology Of Olfactory Sensory Neurons Duringmentioning

confidence: 99%

Distinct Roles of Calcineurin-Nuclear Factor of Activated T-Cells and Protein Kinase A-cAMP Response Element-Binding Protein Signaling in Presynaptic Differentiation

Yoshida¹,

Mishina²

2005

J. Neurosci.

View full text Add to dashboard Cite

Synaptic vesicle accumulation and morphological changes are characteristic features of axon terminal differentiation during synaptogenesis. To investigate the regulatory mechanism that orchestrates synaptic molecules to form mature presynaptic terminals, we visualized a single axon terminal of zebrafish olfactory sensory neurons in vivo and examined the effects of the neuron-specific gene manipulations on the axon terminal differentiation. Synaptic vesicles visualized with vesicle-associated membrane protein 2 (VAMP2)-enhanced green fluorescent protein (EGFP) fusion protein gradually accumulated in axon terminals, whereas the axon terminals visualized with GAP43 fused with EGFP remodeled from complex shapes with filopodia to simple shapes without filopodia from 50 h postfertilization (hpf) to 84 hpf. Expression of dominant-negative protein kinase A (PKA) or cAMP response element-binding protein (CREB) suppressed the VAMP2-EGFP punctum formation in axon terminals during synaptogenesis. Consistently, constitutively active PKA or CREB stimulated VAMP2-EGFP puncta formation. On the other hand, cyclosporine A treatment or suppression of nuclear factor of activated T cells (NFAT) activation prevented the axon terminal remodeling from complex to simple shapes during synaptogenesis. Consistently, expression of constitutively active calcineurin accelerated the axon terminal remodeling. These results suggest that calcineurin-NFAT signaling regulates axon terminal remodeling, and PKA-CREB signaling controls synaptic vesicle accumulation.

show abstract

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.

Cited by 438 publications

References 21 publications

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve

Distinct Roles of Calcineurin-Nuclear Factor of Activated T-Cells and Protein Kinase A-cAMP Response Element-Binding Protein Signaling in Presynaptic Differentiation

Contact Info

Product

Resources

About