Septin6 and Septin7 GTP Binding Proteins Regulate AP-3- and ESCRT-Dependent Multivesicular Body Biogenesis

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