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A mechanism for retromer endosomal coat complex assembly with cargo.

ABSTRACT: Retromer is an evolutionarily conserved protein complex composed of the VPS26, VPS29, and VPS35 proteins that selects and packages cargo proteins into transport carriers that export cargo from the endosome. The mechanisms by which retromer is recruited to the endosome and captures cargo are unknown. We show that membrane recruitment of retromer is mediated by bivalent recognition of an effector of PI3K, SNX3, and the RAB7A GTPase, by the VPS35 retromer subunit. These bivalent interactions prime retromer to capture integral membrane cargo, which enhances membrane association of retromer and initiates cargo sorting. The role of RAB7A is severely impaired by a mutation, K157N, that causes Charcot-Marie-Tooth neuropathy 2B. The results elucidate minimal requirements for retromer assembly on the endosome membrane and reveal how PI3K and RAB signaling are coupled to initiate retromer-mediated cargo export.

SUBMITTER: Harrison MS

PROVIDER: S-EPMC3890810 | biostudies-other | 2014 Jan

REPOSITORIES: biostudies-other

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A mechanism for retromer endosomal coat complex assembly with cargo.

Harrison Megan S MS Hung Chia-Sui CS Liu Ting-ting TT Christiano Romain R Walther Tobias C TC Burd Christopher G CG

Proceedings of the National Academy of Sciences of the United States of America 20131216 1

Retromer is an evolutionarily conserved protein complex composed of the VPS26, VPS29, and VPS35 proteins that selects and packages cargo proteins into transport carriers that export cargo from the endosome. The mechanisms by which retromer is recruited to the endosome and captures cargo are unknown. We show that membrane recruitment of retromer is mediated by bivalent recognition of an effector of PI3K, SNX3, and the RAB7A GTPase, by the VPS35 retromer subunit. These bivalent interactions prime ...[more]

PMID: 24344282

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