Rab proteins are small GTPase proteins that control protein trafficking and degradation and have been implicated in αsyn pathogenesis. Among the Rab proteins, Rab27a and Rab27b are expressed at synaptic terminals in neurons in key brain areas affected in PD and DLB. Rab27s regulate synaptic vesicle exocytosis and recycling. In non-neuronal cells, Rab27s regulate the distal transport of lysosomes. We recently showed elevated Rab27b levels in αsyn models and in human PD and DLB. Additionally, we have shown that Rab27a and Rab27b perturbations can affect αsyn toxicity, potentially through effects on αsyn secretion, clearance, and uptake.

Key questions:

  • Do Rab27s promote autophagic clearance of intracellular αsyn?
  • Do Rab27s regulate secretion of αsyn?
  • Do Rab27s regulate endocytosis of extracellular αsyn?
  • What are the key Rab effectors that mediate Rab27 effects on αsyn?