B‐50 (GAP‐43): Biochemistry and Functional Neurochemistry of a Neuron‐Specific Phosphoprotein

Coggins, Philip J.; Zwiers, H.

doi:10.1111/j.1471-4159.1991.tb11398.x

Cited by 161 publications

(71 citation statements)

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“…Zheng and others suggested that intra-axonal translation of cytoskeletal components was required for sustaining growth cones in regenerating axons (Zheng et al, 2001). GAP43 is a membrane-and cytoskeletal-associated phosphoprotein (Benowitz and Routtenberg, 1987;Skene, 1989;Coggins and Zwiers, 1991) that is expressed at high levels in neurons during development and is concentrated in axonal growth cones (Biffo et al, 1990;Fitzgerald et al, 1991). After neural injury in the adult, however, GAP43 is re-expressed and is rapidly transported along the axons of those neurons where there is successful regeneration (Bisby, 1988;Tetzlaff et al, 1989;Van der Zee et al, 1989;Woolf et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal Expression of SSeCKS in Injured Rat Sciatic Nerve

Chen

Qin

Cheng

et al. 2008

The Anatomical Record

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SSeCKS (src suppressed C kinase substrate) functions in the control of cell signaling and cytoskeletal arrangement. It is expressed in brain and spinal cord, but little is known about its expression in peripheral nerves. In this study, in rats, real-time polymerase chain reaction and Western blot analysis showed that expression of SSeCKS in crushed sciatic nerve reached its highest level 6 hr after crushing, whereas in a transection model, SSeCKS peaked at 2 days in the proximal stump and 12 hr in the distal stump. Immunohistochemical analysis demonstrated up-regulation of SSeCKS protein surrounding the crush site and in the two stumps of the transected nerve. In addition, SSeCKS colocalized with growth-associated protein 43 and with S100, which also changed with time after injury. These findings support the idea that SSeCKS participates in the adaptive response to peripheral nerve injury and may be associated with regeneration. Anat Rec, 291:527-537, 2008Rec, 291:527-537, . 2008 Wiley-Liss, Inc.Key words: SSeCKS; sciatic nerve; crush; transect; rat Src suppressed C kinase substrate (SSeCKS) is a high molecular mass (290/280 kDa) heat-stable protein that was identified as a protein kinase C (PKC) substrate/ PKC-binding protein. In vitro, SSeCKS mRNA and protein levels are down-regulated in transformed cells, suggesting a role in growth regulation (Chapline et al., 1996). In vivo, SSeCKS is expressed by fibroblasts, endothelial cells, and mesangial cells and has mitogenic regulatory activity, indicating a role in tumor suppression. During embryogenesis, SSeCKS is involved in controlling cytoskeletal structure and tissue architecture, forming the migratory process and cell migration (Gelman et al., 2000). The SSeCKS expression pattern is developmentally regulated in numerous cell types and tissues during perinatal growth, indicating a role in development and differentiation processes. In the nervous system of adult rats, SSeCKS is localized to central axonal collaterals of primary sensory neurons in the cerebellum, medulla, and sensory ganglia (including trigeminal ganglia) and in the dorsal horn at all spinal levels. In addition, SSeCKS is localized to C-fibers and is involved in nociception (Siegel et al., 2002). No prior studies have examined the involvement of SSeCKS in peripheral nerve injury; therefore, we examined the expression of SSeCKS in this condition, a complex process that remains poorly understood.Drs. Chen and Qin contributed equally to this work. *Correspondence to: Aiguo Shen, The Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong, People's Republic of China, 226001. Fax: 86-513-85051999. E-mail: shen_aiguo@yahoo.com Abbreviations used: BSA = bovine serum albumin; PBS = phosphate-buffered saline; SSeCKS = src suppressed C kinase substrate; TBST = Tris-buffered saline with Tween; b 2 -M = b 2 -microglobulin; GAP43 = growth-associated protein 43.

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Section: Discussionmentioning

confidence: 99%

Spatiotemporal Expression of SSeCKS in Injured Rat Sciatic Nerve

Chen

Qin

Cheng

et al. 2008

The Anatomical Record

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“…The physiological relevance of intracellular G protein activation by GAP 43 requires additional investigation. Fully processed GAP 43 is located exclusively on the intracellular side of the plasma membrane of neurons [58]. It is expressed at high levels in neuronal growth cones during development and during axonal regeneration where it activates Go which is also enriched in these neuronal compartments [59,60].…”

Section: What Are the Upstream Signaling Partners Of Organelle-associmentioning

confidence: 99%

Potential roles of heterotrimeric G proteins of the endomembrane system

Nürnberg

Ahnert‐Hilger

1996

FEBS Letters

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“…The structure and function relationships of this protein have been reviewed previously [9]. The protein was initially found to be associated with nerve growth [85] and was subsequently purified and characterized [20]. The importance of GAP-43, in general, is shown by the fact that deletion of the GAP-43 gene in mice results in death early in the postnatal period [89].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

Denny

2006

204

166

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GAP-43 is an intracellular growth-associated protein that appears to assist neuronal pathfinding and branching during development and regeneration, and may contribute to presynaptic membrane changes in the adult, leading to the phenomena of neurotransmitter release, endocytosis and synaptic vesicle recycling, long-term potentiation, spatial memory formation, and learning. GAP-43 becomes bound via palmitoylation and the presence of three basic residues to membranes of the early secretory pathway. It is then sorted onto vesicles at the late secretory pathway for fast axonal transport to the growth cone or presynaptic plasma membrane. The palmitate chains do not serve as permanent membrane anchors for GAP-43, because at steady-state most of the GAP-43 in a cell is membrane-bound but is not palmitoylated. Filopodial extension and branching take place when GAP-43 is phosphorylated at Ser-41 by protein kinase C, and this occurs following neurotrophin binding and the activation of numerous small GTPases. GAP-43 has been proposed to cluster the acidic phospholipid phosphatidylinositol 4,5-bisphosphate in plasma membrane rafts. Following GAP-43 phosphorylation, this phospholipid is released to promote local actin filament-membrane attachment. The phosphorylation also releases GAP-43 from calmodulin. The released GAP-43 may then act as a lateral stabilizer of actin filaments. N-terminal fragments of GAP-43, containing 10-20 amino acids, will activate heterotrimeric G proteins, direct GAP-43 to the membrane and lipid rafts, and cause the formation of filopodia, possibly by causing a change in membrane tension. This review will focus on new information regarding GAP-43, including its binding to membranes and its incorporation into lipid rafts, its mechanism of action, and how it affects and is affected by extracellular agents.

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B‐50 (GAP‐43): Biochemistry and Functional Neurochemistry of a Neuron‐Specific Phosphoprotein

Cited by 161 publications

References 128 publications

Spatiotemporal Expression of SSeCKS in Injured Rat Sciatic Nerve

Spatiotemporal Expression of SSeCKS in Injured Rat Sciatic Nerve

Potential roles of heterotrimeric G proteins of the endomembrane system

Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

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