A key regulator of the slow recycling of receptors and lipids that occurs from the endocytic recycling compartment (ERC) back to the cell surface is EHD1. We have recently identified the Rab8a-interacting protein, MICAL-L1, as a novel binding partner for EHD1 that both recruits and interacts with EHD1 on tubular recycling endosomes. MICAL-L1 belongs to the MICALfamily of proteins that are highly expressed in neurons and involved in plexin-mediated repulsive axon guidance. Interestingly, MICAL-L1 contains a coiled coil region in its C-terminus that is both necessary and sufficient for its localization to the EHD1-containing long tubular membranes of the ERC. Furthermore, MICAL-L1-depletion also impaired recycling of both transferrin and integrin receptors from the ERC back to the plasma membrane. In conclusion, our studies implicate MICAL-L1 as a novel regulator of endocytic recycling, and raises the possibility that additional neuronal-expressed proteins may mediate endocytic events in non-neuronal cells.
Keywords: EHD; MICAL; Rab8; endocytic recycling; tubular membranes.