TY - JOUR T1 - <em>rab-27</em> acts in an intestinal secretory pathway to inhibit axon regeneration in <em>C. elegans</em> JF - bioRxiv DO - 10.1101/2020.09.05.283267 SP - 2020.09.05.283267 AU - Alexander T. Lin-Moore AU - Motunrayo J. Oyeyemi AU - Marc Hammarlund Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/09/10/2020.09.05.283267.abstract N2 - Injured axons must regenerate to restore nervous system function, and regeneration is regulated in part by external factors from non-neuronal tissues. Many of these extrinsic factors act in the immediate cellular environment of the axon to promote or restrict regeneration, but the existence of long-distance signals regulating axon regeneration has not been clear. Here we show that the Rab GTPase rab-27 inhibits regeneration of GABAergic motor neurons in C. elegans through activity in the intestine. Re-expression of RAB-27, but not the closely related RAB-3, in the intestine of rab-27 mutant animals is sufficient to rescue normal regeneration. Several additional components of an intestinal neuropeptide secretion pathway also inhibit axon regeneration, including NPDC1/cab-1, SNAP25/aex-4, and KPC3/aex-5. Together these data indicate that RAB-27-dependent neuropeptide secretion from the intestine inhibits axon regeneration, and point to distal tissues as potent extrinsic regulators of regeneration.Competing Interest StatementThe authors have declared no competing interest. ER -