Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent multivesicular body biogenesis

Sofia Traikov, Christoph Stange, Thomas Wassmer, Perrine Paul-Gilloteaux, Jean Salamero, Graça Raposo, Bernard Hoflack

Research output: Contribution to journalArticle

Abstract

Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton and membrane organization, cell division and host/pathogen interactions. The precise function of many family members remains elusive. We show that SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3 membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP interactions also influence the membrane interaction of ESCRT (endosomal-sorting complex required for transport)-I, which selects ubiquitinated cargos for degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7 function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane domains, they uncover an unsuspected coordination of these sorting machineries during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3 interactor regulating ESCRT-I sorting activity and whose mutations are linked with Charcot-Marie-Tooth neuropathies.

Original languageEnglish
Article numbere109372
Number of pages12
JournalPLoS ONE
Volume9
Issue number11
DOIs
Publication statusPublished - 7 Nov 2014

Bibliographical note

Copyright: © 2014 Traikov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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    Traikov, S., Stange, C., Wassmer, T., Paul-Gilloteaux, P., Salamero, J., Raposo, G., & Hoflack, B. (2014). Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent multivesicular body biogenesis. PLoS ONE, 9(11), [e109372]. https://doi.org/10.1371/journal.pone.0109372