Axon regeneration is a conserved property of neurons, but the cellular mechanisms that control regeneration are incompletely understood. We have found that
rab-27 is a novel, cell intrinsic inhibitor of regeneration. Loss of
rab-27 improves regeneration initiation and regrowth in GABAergic DD/VD neurons. Re-expression of
rab-27 in the GABA neurons of null animals restores normal regeneration.
rab-27 encodes a small GTPase known to regulate vesicle tethering and fusion.
rab-27 was previously shown to act redundantly with
rab-3 through the common effector Rabphilin to promote synaptic vesicle transmission (Mahoney et al. 2006). We find that loss of either
rab-3 or Rabphilin does not affect regeneration, and that loss of either
rab-3 or Rabphilin suppresses the high regeneration phenotype of
rab-27 mutants. These data suggest that the common function of
rab-27,
rab-3, and Rabphilin in synaptic vesicle tethering facilitates regeneration. At the same time, these data suggest a unique role for
rab-27 independent of
rab-3 and Rabphilin to inhibit regeneration, possibly by regulating fusion of dense core vesicles or other vesicle types. Together, our findings point to a complex role for
rab-27 as a regulator of regeneration. Understanding the cell biological functions of
rab-27 in regeneration may identify specific mechanisms that limit the ability of neurons to respond to injury. Mahoney, T. R., Q. Liu, T. Itoh, S. Luo, G. Hadwiger, R. Vincent, Z. W. Wang, M. Fukuda, & M. L. Nonet. 2006. Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans. Mol Biol Cell. 17: 2617-2625.