Changes in the distribution of GAP-43 during the development of neuronal polarity

Goslin, Kimberly; Schreyer, David J.; Skene, J. H. Pate; Banker, Gary

doi:10.1523/jneurosci.10-02-00588.1990

Cited by 209 publications

(96 citation statements)

References 41 publications

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“…Both are functionally implicated in axon terminal remodeling within the striatum, but these proteins are synthesized within cortical somata of corticostriatal neurons. Consistent with our findings, both proteins accrue within the somata of corticostriatal neurons, as well as along fibers and in growth cones (Goslin et al, 1990,Gavet et al, 1998. GAP-43 protein and mRNA appear to be axonally transported, suggesting that somatic induction may be followed by distal distribution.…”

Section: Discussionsupporting

confidence: 92%

Intrastriatal dopamine D1 antagonism dampens neural plasticity in response to motor cortex lesion

2007

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Motor cortex lesions in rats partially denervate the striatum, producing behavioral deficits and inducing reactive neuroplasticity. Plastic responses include changes in growth-associated protein marker expression and anatomical restructuring. Corticostriatal plasticity is dependent on dopamine at the striatal target, where D1 receptor signaling reinforces behaviorally relevant neural activity. To determine whether striatal dopamine D1 receptor signaling is important for the growth-associated protein responses and behavioral recovery that follow unilateral motor cortex aspiration, the dopamine D1 receptor antagonist SCH23390 was intrastriatally infused in cortically lesioned animals. After a cortical aspiration lesion in Long Evans rats, the growth-associated proteins SCG10 and GAP-43 were upregulated in the cortex contralateral to the lesion at 30 days post-lesion. However, continuous unilateral intrastriatal infusion of SCH23390 prevented this aspiration-induced upregulation. Furthermore, lesioned rats demonstrated spontaneous sensorimotor improvement, in terms of limb-use symmetry, about one month post-lesion. This improvement was prevented with chronic intrastriatal SCH23390 infusion. The D1 receptor influence may be important to normalize corticostriatal activity (and observable behavior), either in a long-term manner or temporarily until other more permanent means of synaptic regulation, such as sprouting or synaptogenesis, may be implemented. Keywords cortical ablation; striatum; SCH23390The ability to reorganize neural connections according to changing environmental cues is essential to the formation of the wide network of limbic, striatal, and cortical circuits that regulate the complex array of human behaviors. Generally referred to as neural plasticity, these adaptive processes are most obvious in the developing brain, but are also utilized throughout adulthood as new skills and memories are acquired. Likewise, when the brain is damaged by trauma or disease, adaptive mechanisms of plasticity are brought into play and are critical for determining the limits of functional recovery (Ivanco and Greenough, 2000,Johansson, 2000,Nudo et al., 2001,Gonzalez and Kolb, 2003. These adaptive processes are governed by local extra-and intracellular signals and can be manipulated by various experimental interventions including: exercise (Cotman and Berchtold, 2002,Gomez-Pinilla et al., 2002) Tel: 323-442-2126; Fax: 323-442-2127. E-mail address: elizabjd@usc.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (van Praag et al., 2000), motor skills training (Plautz et a...

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Section: Discussionsupporting

confidence: 92%

Intrastriatal dopamine D1 antagonism dampens neural plasticity in response to motor cortex lesion

2007

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“…Initially, the protein is equally distributed among all growth cones in the neuron, but reactivity is decreased in all other neurites when neuronal polarity is established and one outgrowth becomes classifiable as an axon (Goslin et al, 1990). It has been shown that developing RGCs express GAP-43 (Avwenagha et al, 2003;Ekstrom and Johansson, 2003), and expression of the gene plays an important role in axonal growth and guidance in forming appropriate tectal connections in the brain (Strittmatter et al, 1995;Zhu and Julien, 1999).…”

Section: Introductionmentioning

confidence: 99%

Induction of axon and dendrite formation during early RGC-5 cell differentiation

Lieven¹,

Millet²,

Hoegger³

et al. 2007

Experimental Eye Research

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The retinal ganglion cell (RGC)-like RGC-5 line can be differentiated with staurosporine to stop dividing, extend neurites, and increase levels of several ganglion cell markers. This allows study of regulation of neurite development on a single cell basis. However, it is unclear whether the neurites induced by differentiation have features characteristic of dendrites or axons. To address this question, RGC-5 cells were differentiated with staurosporine and then immunoblotted for microtubuleassociated protein 2 (MAP2) and actin, or stained immunocytochemically for different MAP2 isoforms, tau, growth-associated protein 43 (GAP-43), or the neuronal marker β-III-tubulin. We found that staurosporine-induced differentiation led to an upregulation of MAP2c, a MAP2 isoform expressed in developing neurons. Some neurites expressed MAP2c but not the dendritic markers MAP2a and b, consistent with an axonal phenotype. Some neurites expressed the axonal marker tau in a characteristic proximal-to-distal gradient, and had GAP-43 labeling characteristic of axonal growth cones. The presence of MAP2c in differentiated RGC-5 cells is indicative of RGC-like neurite development, and the pattern of staining for the different MAP2 isoforms, as well as positivity for tau and GAP-43, indicates that differentiation induces axon-like and dendrite-like neurites.

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“…GAP-43 (also known as neuromodulin, B-50, F1, and P57) is enriched in the growth cone membranes of elongating axons (5)(6)(7)(8)(9) and is proposed to function in neuronal plasticity and the regulation of neurotransmitter release (10 -13). GAP-43 is initially synthesized as a soluble protein, which subsequently passes through the secretory pathway, and becomes membrane-bound post-translationally.…”

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confidence: 99%

Mass Spectrometric Analysis of GAP-43/Neuromodulin Reveals the Presence of a Variety of Fatty Acylated Species

Liang

Neubert

et al. 2002

Journal of Biological Chemistry

101

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GAP-43 (neuromodulin) is a protein kinase C substrate that is abundant in developing and regenerating neurons. Thioester-linked palmitoylation at two cysteines near the GAP-43 N terminus has been implicated in directing membrane binding. Here, we use mass spectrometry to examine the stoichiometry of palmitoylation and the molecular identity of the fatty acid(s) attached to GAP-43 in vivo. GAP-43 expressed in either PC12 or COS-1 cells was acetylated at the N-terminal methionine. Approximately 35% of the N-terminal GAP-43 peptides were also modified by palmitate and/or stearate on Cys residues. Interestingly, a variety of acylated species was detected, in which one of the Cys residues was acylated by either palmitate or stearate, or both Cys residues were acylated by palmitates or stearates or a combination of palmitate and stearate. Depalmitoylation of membrane-bound GAP-43 did not release the protein from the membrane, implying that additional forces function to maintain membrane binding. Indeed, mutation of four basic residues within the N-terminal domain of GAP-43 dramatically reduced membrane localization of GAP-43 without affecting palmitoylation. These data reveal the heterogeneous nature of S-acylation in vivo and illustrate the power of mass spectrometry for identification of key regulatory protein modifications.Covalent modification by acetylation or fatty acylation occurs on a variety of viral and cellular proteins (1). N-terminal acetylation is one of the most common protein modifications, occurring on ϳ85% of eukaryotic proteins (2). The amino acid residue adjacent to the amino-terminal methionine residue determines whether the N-terminal methionine is retained or removed before acetylation (2). Proteins that contain the Nterminal sequence MGXXX(S/T) undergo a different set of modifications. The initiating Met is removed, and myristate is added to the N-terminal glycine. The requirement for glycine at the N terminus is absolute for N-myristoylation to occur.In contrast to N-terminal acetylation and myristoylation, which occur co-translationally, palmitoylation is a post-translational lipid modification. Nearly all palmitoylated proteins are S-acylated by attachment of palmitate via a thioester linkage to the sulfhydryl group of cysteine. Exceptions include adenylate cyclase toxin from Bordetella pertussis, which is modified by amide-linked palmitoylation on the ⑀-amino group of lysine residues (3) and human sonic hedgehog, which is palmitoylated through an amide linkage to the N-terminal cysteine (4). Unlike myristoylation, the enzymology of palmitoylation reactions is poorly understood. Palmitoylacyl transferases have not been thoroughly purified and characterized. Moreover, no study has directly examined the nature of thioester-linked palmitoylation in vivo at a molecular level. All of the studies on thioester-linked palmitoylation are based on incorporation of radioactive palmitate. The stoichiometry of palmitoylation as well as the molecular identity of the attached fatty acid moiety (palmitate a...

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Changes in the distribution of GAP-43 during the development of neuronal polarity

Cited by 209 publications

References 41 publications

Intrastriatal dopamine D1 antagonism dampens neural plasticity in response to motor cortex lesion

Intrastriatal dopamine D1 antagonism dampens neural plasticity in response to motor cortex lesion

Induction of axon and dendrite formation during early RGC-5 cell differentiation

Mass Spectrometric Analysis of GAP-43/Neuromodulin Reveals the Presence of a Variety of Fatty Acylated Species

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