Abstract
Expression of the adaptor protein v-Crk in PC12 cells results in sustained activation of NGF signaling pathways and augmented neuritogenesis. However, the inhibitory effect of the v-Crk SH2 domain mutant on neurite elongation does not correlate with impaired Trk A dependent signaling events or gene induction. In contrast, immunofluorescence studies and Triton X-100 extraction experiments indicate that v-Crk co-localizes with the cytoskeletal protein paxillin in the actin cytoskeleton whereas the v-Crk SH2 mutant causes aberrant aggregration of actin filaments at the growth cones. Interestingly, the neurotrophin receptor p75 in v-CrkPC12 cells also displays enhanced localization to the cytoskeleton and these cells exhibit an increased rate of NGF internalization. Together our data suggest that v-Crk might target the NGF-activated receptor signaling complex to the cytoskeleton, thereby potentiating neuritogenesis at the growth cone level. However, mutation in the v-Crk SH2 domain uncouples NGF signaling from the cytoskeletal interactions necessary for neurite elongation.
Original language | English |
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Pages (from-to) | 157-170 |
Number of pages | 14 |
Journal | Molecular and Cellular Neurosciences |
Volume | 8 |
Issue number | 2-3 |
DOIs | |
Publication status | Published - Aug 1996 |
Bibliographical note
Funding Information:We thank JL Photo/First Foto (New York) for excellent technical assistance. This work was supported by Public Health Service awards to B.L.H. (NS 30687) and R.B.B. (GM51446) and by the American Health Assistance Foundation (B.L.H.). J.C.C. is supported by Tri-Institutional Vision Training Grant (T32 EYO7138).
Funding
We thank JL Photo/First Foto (New York) for excellent technical assistance. This work was supported by Public Health Service awards to B.L.H. (NS 30687) and R.B.B. (GM51446) and by the American Health Assistance Foundation (B.L.H.). J.C.C. is supported by Tri-Institutional Vision Training Grant (T32 EYO7138).