The kinase c substrate protein b-50 and axonal regeneration

Verhaagen, Joost; Hooff, C. O. M. Van; Edwards, P.M.; Graan, P.N.E. de; Oestreicher, A.B.; Schotman, P.; Jennekens, F.G.I.; Gispen, W.H.

doi:10.1016/0361-9230(86)90084-5

Cited by 85 publications

(37 citation statements)

References 31 publications

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“…The expression of the growth-associated protein B-50/GAP-43 in the adult PNS is relatively low compared to that of the CNS (Verhaagen et al, 1986;Tetzlaff et al, 1989;Verkade et al, 1995). Injury to the peripheral nerves results in a rapid upregulation of the expression of B-50/GAP-43 ( Van der Zee et al, 1989; * To whom correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural evidence for the lack of co-transport of B-50/GAP-43 and calmodulin in myelinated axons of the regenerating rat sciatic nerve

et al. 1996

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Following peripheral nerve injury, neurons respond with synthesis of proteins required for axonal regeneration. Newly synthesized membrane proteins, like B-50/GAP-43, are transported with the fast component of anterograde axonal transport. Structural proteins and calmodulin are transported by the slow component. Since B-50/GAP-43 can bind calmodulin, it has been hypothesised that B-50/GAP-43 may act as a carrier for fast anterograde transport of calmodulin, so that both proteins are delivered rapidly to the distally outgrowing axons ('the fast carrier hypothesis'). We have investigated whether this hypothesis is valid in myelinated axons of the regenerating rat sciatic nerve. Seven days after crush, the nerve was ligated to accumulate fast transported proteins. Nerve pieces were dissected proximal to the ligation and processed for immunofluorescence and quantitative electron microscopy by postembedding single and double immunogold labelling. By light microscopy, we observed a qualitative increase in B-50/GAP-43 immunofluorescence in the axonal element immediately proximal to the nerve ligation (termed 'accumulated') compared to an upstream site (termed 'regenerating') closer to the cell body. The immunofluorescence for calmodulin appeared to be the same at both sites. Using electron microscopy, we observed that organelles had collected at the 'accumulated' site, moreover the density of B-50/GAP-43 immunolabelling was significantly increased compared to the 'regenerating' site, where the axoplasmic structure was undisturbed. The increase in B-50/GAP-43 immunolabelling was largely associated with vesicles. The density of calmodulin immunolabelling was similar at both sites. Approximately 25% of the total B-50/GAP-43 was associated with vesicles of which only 15% also contained labelling for calmodulin. Thus, ligation of the nerve resulted in accumulation of vesicles, including those carrying B-50/GAP-43, largely without calmodulin. Therefore, contrary to 'the fast carrier hypothesis', the bulk of calmodulin is not co-transported with B-50/GAP-43 in myelinated axons of the sciatic nerve.

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Section: Introductionmentioning

confidence: 99%

Ultrastructural evidence for the lack of co-transport of B-50/GAP-43 and calmodulin in myelinated axons of the regenerating rat sciatic nerve

et al. 1996

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“…This protein is a prominent substrate to protein kinase C in growth cones membranes and outgrowing neurites in fetal and postnatal rat brain [2, 15,18] and in outgrowing processes of differentiated PC12 cells [26]. By means of radioimmunoassay for B-50 [l 6], the highest levels of B-50 are determined in developing nervous systems and in regenerating axons following lesion of peripheral nerve [27,28]. From these studies, it is apparent that the B-50 (GAP43) protein can be used as a selective marker of neurite outgrowth in developing neural tissue.…”

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confidence: 99%

Immunocytochemical distribution of the protein kinase C substrate B-50 (GAP43) in developing rat pyramidal tract

Gorgels

Oestreicher

Kort

et al. 1987

Neuroscience Letters

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The neuron-specific phosphoprotein B-50 is a major substrate of kinase C in fetal nerve growth cones, neonatal neural and synaptosomal plasma membranes. B-50 is identical to a growth-associated protein GAP43. Similarly, increases in B-50 occur during rat brain development, neuronal differentiation and axon regeneration. To document the relation between the expression of B-50 and the outgrowth of central axons, we studied B-50 in the developing pyramidal tract in rats at postnatal days 2, 7 and 90 (P2, P7 and P90), at the third cervical spinal segment C3, using affinity-purified antibodies to B-50. At P2 and P7, when outgrowth of pyramidal tract fibers is occurring, B-50 immunoreactivity (BIR) is intense in these fibers. BIR is reduced from P2 to P7 in the ascending fiber tracts of the cuneatus and the gracilis, which develop earlier. At P90 when most of the dorsal funiculus fibers have reached their targets and many are myelinated, BIR is dramatically reduced. In agreement, a 10-fold decrease in B-50 content was measured at P90, as compared to P7. Therefore, our results indicate that B-50 is only expressed relatively abundant in axons of the funiculus posterior during outgrowth. By inference, B-50 may be a differentiating marker to detect elongating fibers.The ontogenesis of the spinal pyramidal tract in the rat occurs during the postnatal development. Shortly after birth, the leading corticospinal fibers are entering the upper cervical segments of the spinal cord [21], where they occupy the most ventral part of the dorsal funiculus. The spatial and temporal outgrowth of these corticospinal fibers in the spinal white and gray matter in the neonatal rat have been described by Gribnau et al. [8]. They demonstrated that the corticospinal fibers have reached the upper thoracic segments of the spinal cord at postnatal day 2 (P2) and the sacral segments at P7. A delay of two days was observed between the arrival of the corticospinal axons at a given spinal cord level and their outgrowth into the adjacent spinal

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“…This protein is abundantly distributed in developing and regenerating neurons and transported to the growth cones during axonal outgrowth (Jacobson et al, 1986;Skene and Willard, 1981;Verhaagen et al, 1986). The synthesis is repressed or down-regulated following synaptogenesis and target innervation, but increases during axon regeneration Mehta et al, 1993;Sommervaille et al, 1991;Tetzlaff et al, 1989;Verhaagen et al, 1986Verhaagen et al, , 1988Woolf et al, 1990Woolf et al, , 1992.…”

Section: Growth-associated Protein-43 (Gap-43)mentioning

confidence: 99%

Regeneration of periodontal Ruffini endings in adults and neonates

Wakisaka

Atsumi

2003

Microscopy Res & Technique

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We reviewed the regeneration of periodontal Ruffini endings, primary mechanoreceptors in the periodontal ligament, following injury to the inferior alveolar nerve (IAN) in adult and neonatal rats. Morphologically, mature Ruffini endings are characterized by an extensive arborization of axonal terminals and association with specialized Schwann cells, called lamellar or terminal Schwann cells. Following injury to IAN in the adult, the periodontal Ruffini endings of the rat lower incisor ligament regenerate more rapidly than Ruffini endings in other tissues. During regeneration, terminal Schwann cells migrate into regions where they are never found under normal conditions. The development of periodontal Ruffini endings of the rat incisor is closely associated with the eruption of the teeth; the morphology and distribution of the terminal Schwann cells became almost identical to those in adults during postnatal days 15-18 (PN 15-18d) when the first molars appear in the oral cavity, while the axonal elements showed extensive ramification around PN 28d when the functional occlusion commences. When the IAN was injured in neonates, the regeneration of periodontal Ruffini endings was delayed compared with the adults. The migration of terminal Schwann cells is also observed following IAN injury, after which the distribution of terminal Schwann cells became almost identical to that of the adults, i.e., PN 14d. Since the interaction between axon and Schwann cell is important during regeneration and development, further studies are required to elucidate its molecular mechanism during the regeneration as well as the development of the periodontal Ruffini endings.

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The kinase c substrate protein b-50 and axonal regeneration

Cited by 85 publications

References 31 publications

Ultrastructural evidence for the lack of co-transport of B-50/GAP-43 and calmodulin in myelinated axons of the regenerating rat sciatic nerve

Ultrastructural evidence for the lack of co-transport of B-50/GAP-43 and calmodulin in myelinated axons of the regenerating rat sciatic nerve

Immunocytochemical distribution of the protein kinase C substrate B-50 (GAP43) in developing rat pyramidal tract

Regeneration of periodontal Ruffini endings in adults and neonates

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