Identification of a RAB32-LRMDA-Commander membrane trafficking complex reveals the molecular mechanism of human oculocutaneous albinism type 7.

ABSTRACT: The endosomal Commander assembly associates with the sorting nexin-17 (SNX17) cargo adaptor to regulate cell surface recycling of internalised integral proteins including integrins and lipoprotein receptors. Here, we identify leucine rich melanocyte differentiation associated (LRMDA) as a Commander binding protein. We reveal that LRMDA and SNX17 share a common mechanism of Commander association, and that LRMDA simultaneously associates with Commander and active RAB32, establishing distinct RAB32-LRMDA-Commander and SNX17-Commander assemblies. Functional analysis in melanocytes reveals distinct roles for RAB32-LRMDA-Commander and SNX17-Commander in melanosome biogenesis. We reveal how LRMDA mutations, causative for oculocutaneous albinism type 7, a hypopigmentation disorder accompanied by p

SUBMITTER: Butkovic R 

PROVIDER: S-EPMC12491506 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature