Molecular analysis of the function of the neuronal growth-associated protein GAP-43 by genetic intervention

Molecular Neurobiology - Tập 5 - Trang 131-141 - 1991
Rachael L. Neve1, Kathryn J. Ivins1, Larry I. Benowitz2, Matthew J. During3, Alfred I. Geller4
1Department of Psychobiology, University of California, Irvine
2Department of Surgery, The Children's Hospital, Boston
3Department of Neurosurgery, Yale University School of Medicine, New Haven
4Department of Endocrinology, The Children's Hospital, Boston

Tóm tắt

GAP-43 is a presynaptic membrane phosphoprotein that has been implicated in both the development and the modulation of neural connections. The availability of cDNA clones for GAP-43 makes it possible to examine with greater precision its role in neuronal outgrowth and physiology. We used Northern blots andin situ hybridization with GAP-43 antisense RNA probes to show that GAP-43 is expressed selectively in associative regions of the adult brain. Immunocytochemical analyses showed alterations in the pattern of GAP-43 expression in the hippocampus during reactive synaptogenesis following lesions of the perforant pathway. Genetic intervention methodology was used to analyze the molecular nature of GAP-43 involvement in synaptic plasticity. GAP-43-transfected PC12 cells displayed an enhanced response to nerve growth factor, suggesting that GAP-43 may be directly involved in neurite extension and in the modulation of the neuronal response to extrinsic trophic factors. Studies of PC12 cell transfectants, in which the synthesis of GAP-43 was blocked by expression of GAP-43 antisense RNA, showed that evoked dopamine release was significantly attenuated in these cells. The use of gene transfer into neurons with the HSV-1 vector is presented as a method of analyzing the interaction of GAP-43 with signal transduction systems during neurotransmitter release.

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Molecular Neurobiology

Tập 5

131-141

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