RT Journal Article
SR Electronic
T1 Prenylation of axonally translated proteins controls NGF-dependent axon growth
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.21.914606
DO 10.1101/2020.01.21.914606
A1 Emily Scott-Solomon
A1 Rejji Kuruvilla
YR 2020
UL http://biorxiv.org/content/early/2020/01/22/2020.01.21.914606.abstract
AB 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.