Biology

Dr. Subbarao Gangi Setty
Department of Microbiology & Cell Biology Indian Institute of Science, Bangalore

Abstract:

Sorting and recycling endosomes (S/REs) are transient intermediate organelles of endocytic/secretory process, regulates cargo sorting/recycling and contribute to the maturation/function of lysosomes in all cells and lysosome-related organelles (LROs) in specialized cells. However, the mechanism of RE biogenesis from SEs is largely unknown. Using RNAi screen, we have identified small G-protein, Rab22A that controls the RE dynamics and organelle biogenesis by forming unique multi-subunit protein complex on SE membranes. Our study demonstrated that Rab22A promotes the assembly of a multi-subunit endosomal complex with BLOC-1, BLOC-2 and KIF13A on early/SEs and generates long tubular endosomal intermediates, which deliver the cargo to cell surface or LROs. Consistently, mutation or depletion of any components of these two complexes result in severe hypopigmentation or genetic disease namely Hermansky-Pudlak syndrome (HPS). Taken together, our findings illustrated a novel mechanism on endocytic organelles that maintain cellular and organelle homeostasis.