Isolation and characterization of protrudin, a master regulator of neurite formation

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Guanosine triphosphatases (GTPases) of the Rab family are key regulators of membrane trafficking, with Rab11 playing a specific role in membrane recycling. We identified a protein, protrudin, that promoted neurite formation through interaction with the guanosine diphosphate (GDP)-bound form of Rab11. Phosphorylation of protrudin by extracellular signal-regulated kinase (ERK) in response to nerve growth factor promoted its association with Rab11-GDP. Down-regulation of protrudin by RNA interference induced membrane extension in all directions and inhibited neurite formation. Thus protrudin regulates Rab11-dependent membrane recycling to promote the directional membrane trafficking required for neurite formation.