The mechanisms of the biosynthesis of nerve growth factor (NGF) and of the two other subunits with which it is associated in the high molecular weight complex will be explored in in vitro incorporation experiments in submaxillary gland slices and in cell-free synthesizing systems translating RNA from the gland. The identity of the primary translation product of the NGF gene and the specificity of its processing will be examined. The interaction of NGF with its specific receptors on sympathetic and sensory neurons will be compared with the interactions on PC12 cells. The time course of the internalization of NGF and of its lysosomal degradation or transport to the nucleus will be determined for PC12 cells in suspension and on plates. Attempts will be made to correlate nuclear binding with initiation of neurite outgrowth and to characterize the way in which cyclic AMP is partly able to mimic NGF.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS004270-23
Application #
3393321
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1975-12-01
Project End
1985-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
23
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Yamauchi, Junji; Miyamoto, Yuki; Tanoue, Akito et al. (2005) Ras activation of a Rac1 exchange factor, Tiam1, mediates neurotrophin-3-induced Schwann cell migration. Proc Natl Acad Sci U S A 102:14889-94
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Yamauchi, Junji; Chan, Jonah R; Shooter, Eric M (2004) Neurotrophins regulate Schwann cell migration by activating divergent signaling pathways dependent on Rho GTPases. Proc Natl Acad Sci U S A 101:8774-9
Tolwani, Ravi J; Cosgaya, Jose M; Varma, Sushama et al. (2004) BDNF overexpression produces a long-term increase in myelin formation in the peripheral nervous system. J Neurosci Res 77:662-9
Cosgaya, Jose M; Chan, Jonah R; Shooter, Eric M (2002) The neurotrophin receptor p75NTR as a positive modulator of myelination. Science 298:1245-8
Ryan, Mary C; Shooter, Eric M; Notterpek, Lucia (2002) Aggresome formation in neuropathy models based on peripheral myelin protein 22 mutations. Neurobiol Dis 10:109-18

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