An ABCG Transporter Functions in Rab Localization and Lysosome-Related Organelle Biogenesis in Caenorhabditis elegans

ABC transporters couple ATP hydrolysis to the transport of substrates across cellular membranes. This protein superfamily has diverse activities resulting from differences in their cargo and subcellular localization. Our work investigates the role of the ABCG family member WHT-2in the biogenesis of gut granules, a Caenorhabditis eleganslysosome-related organelle. In addition to being required for the accumulation of birefringent material within gut granules, WHT-2is necessary for the localization of gut granule proteins when trafficking pathways to this organelle are partially disrupted. The role of WHT-2in gut granule protein targeting is likely linked to its function in Rab GTPase localization. We show that WHT-2promotes the gut granule association of the Rab32 family member GLO-1and the endolysosomal RAB-7, identifying a novel function for an ABC transporter. WHT-2localizes to gut granules where it could play a direct role in controlling Rab localization. Loss of CCZ-1and GLO-3, which likely function as a guanine nucleotide exchange factor (GEF) for GLO-1, lead to similar disruption of GLO-1localization. We show that CCZ-1, like GLO-3, is localized to gut granules. WHT-2does not direct the gut granule association of the GLO-1GEF and our results point to WHT-2functioning differently than GLO-3and CCZ-1. Point mutations in WHT-2that inhibit its transport activity, but not its subcellular localization, lead to the loss of GLO-1from gut granules, while other WHT-2activities are not completely disrupted, suggesting that WHT-2functions in organelle biogenesis through transport-dependent and transport-independent activities.