Hsc70 chaperone activity underlies Trio GEF function in axon growth and guidance induced by netrin-1.
Bottom Line: Hsc70 dynamically associated with the N-terminal region and Rac1 GEF domain of Trio.Whereas Hsc70 expression supported Trio-dependent Rac1 activation, adenosine triphosphatase-deficient Hsc70 (D10N) abrogated Trio Rac1 GEF activity and netrin-1-induced Rac1 activation.Hsc70 was required for netrin-1-mediated axon growth and attraction in vitro, whereas Hsc70 activity supported callosal projections and radial neuronal migration in the embryonic neocortex.
Affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 0C7, Canada The Research Institute of McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.Show MeSH
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Mentions: Because Hsc70 is a molecular chaperone, we assessed whether it may function to regulate Trio localization within cortical growth cones. To first establish Trio localization, cortical neurons were treated with netrin-1 for 5 min, and then fixed and stained (Fig. 3 A). Trio and F-actin growth cone localizations were assessed and the intensity of each signal was measured along a 10-µm segment of the distal growth cone (Fig. 3 A, right). Upon netrin-1 treatment, the intensity of Trio shifted to the growth cone periphery compared with untreated growth cones, similar to F-actin (Fig. 3, A and B).
Affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 0C7, Canada The Research Institute of McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.