Dissociation of NGF induced signal transduction from neurite elongation by expression of a mutant adaptor protein v-Crk in PC12 cells

Kenneth K. Teng*, Jody C. Courtney, Paul Van Bergen En Henegouwen, Raymond B. Birge, Barbara L. Hempstead

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    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 languageEnglish
    Pages (from-to)157-170
    Number of pages14
    JournalMolecular and Cellular Neurosciences
    Volume8
    Issue number2-3
    DOIs
    Publication statusPublished - 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).

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