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.

间隔信号对于神经元的细胞组织和功能结果的特异性至关重要。在这里，我们报告轴突区室中新合成的蛋白质的翻译后脂化允许对外部信号的短期和自主反应。使用条件突变小鼠，我们发现蛋白异戊二烯化对于目标器官的交感神经轴突神经支配是必不可少的。我们确定了交感神经轴突中的异戊二烯化的本地化要求，以促进对神经营养蛋白，神经生长因子（NGF）的轴突生长。NGF触发轴突中包括Rac1 GTPase在内的蛋白质的异戊二烯化，这与典型的异戊二烯化本构性观点（以惊人的方式取决于轴突蛋白合成）相反。新的异戊二烯化蛋白在轴突中定位于携带TrkA的内体，并促进轴突生长所需的受体运输。因此，异戊二烯基化与局部蛋白质合成的耦合为神经元发育过程中空间分离的细胞功能提供了一种机制。