Dense core-vesicle mobility is regulated by Rab11a

Neurosecretion is a fundamental and tightly regulated process, occurring in specialized cells, like neurons and neuroendocrine cells,which is affected in neurodegenerative diseases. Understanding its regulation can help find new targets to fight these diseases. Rab11a is a small GTPase classically involved in constitutive recycling pathways. However, its role in the secretory pathway of neuroendocrine cells remains unclear. Our previous data showed that Rab11a regulates neurosecretion in chromaffin cells, a well known cellular model for neurosecretion. Here, we followed secretory vesicle trafficking using fluorescently-tagged neuropeptide Y, a natural cargo of these vesicles, transfected to chromaffin cells. Co-transfection of Rab11a, either WT or its mutant forms with impaired GTP/GDP cycle, induced a reduction in the amount of peripheral NPY. Moreover, during unstimulated conditions, Rab11a inactive mutant decreased secretory vesicle mobility compared to Rab11a-WT overexpressing cells, while Rab11a active mutant increased speed and total distance traveled. In K+-stimulated chromaffin cells, both inactive and active mutants decreased secretory vesicle mobility, showing vesicle trajectories with reduced speed compared to Rab11a-WT overexpressing cells. We propose that Rab11a activity plays a fundamental role in neurosecretion by modulating the availability of secretory vesicles at the plasma membrane through the regulation of the vesicular trafficking in chromaffin cells.