Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation.

ABSTRACT: Endosomal retrieval and recycling of integral cargo proteins is essential for cell and organism development and homeostasis and is orchestrated through a specialised endosomal nanodomain, the retrieval sub-domain. Sub-domain dysfunction is associated with human disease, but our mechanistic understanding of its function remains poorly described. Here, using proximity proteomics of retrieval sub-domain components Retromer and Retriever we identify mechanistic details of retrieval sub-domain composition and organization, including an unrecognised complexity in the interface with RAB GTPase switching. Combining X-ray crystallography and in silico predictions with biochemical and cellular analysis, we reveal that Retromer directly associates and recruits the RAB10 regulators DENND4A, DENND4C, T

SUBMITTER: Anton-Plagaro C 

PROVIDER: S-EPMC12311110 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature