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Publication : Prenylation of Axonally Translated Rac1 Controls NGF-Dependent Axon Growth.

First Author  Scott-Solomon E Year  2020
Journal  Dev Cell Volume  53
Issue  6 Pages  691-705.e7
PubMed ID  32533921 Mgi Jnum  J:290861
Mgi Id  MGI:6437722 Doi  10.1016/j.devcel.2020.05.020
Citation  Scott-Solomon E, et al. (2020) Prenylation of Axonally Translated Rac1 Controls NGF-Dependent Axon Growth. Dev Cell 53(6):691-705.e7
abstractText  Compartmentalized signaling is critical for cellular organization and specificity of functional outcomes in neurons. Here, we report that post-translational lipidation of newly synthesized proteins in axonal compartments allows for short-term and autonomous responses to extrinsic cues. Using conditional mutant mice, we found that protein prenylation is essential for sympathetic axon innervation of target organs. We identify a localized requirement for prenylation in sympathetic axons to promote axonal growth in response to the neurotrophin, nerve growth factor (NGF). NGF triggers prenylation of proteins including the Rac1 GTPase in axons, counter to the canonical view of prenylation as constitutive, and strikingly, in a manner dependent on axonal protein synthesis. Newly prenylated proteins localize to TrkA-harboring endosomes in axons and promote receptor trafficking necessary for axonal growth. Thus, coupling of prenylation to local protein synthesis presents a mechanism for spatially segregated cellular functions during neuronal development.
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