title: Dissociation of NGF Induced Signal Transduction from Neurite Elongation by Expression of a Mutant Adaptor Protein v-Crk in PC12 Cells
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.
authors.affiliation: Division of Hematology-Oncology, Cornell University Medical College, New York, New York, 10021
authors.initials: KK
authors.lastname: Teng
authors.initials: JC
authors.lastname: Courtney
authors.initials: PB
authors.lastname: Henegouwen
authors.initials: RB
authors.lastname: Birge
authors.initials: BL
authors.lastname: Hempstead