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

Sofia Traikov (1) , Christoph Stange (1) , Thomas Wassmer (1, 2) , Perrine Paul-Gilloteaux (3, 4) , Jean Salamero (3, 4) , Graça Raposo (1) , Bernard Hoflack (1)

1 TU Dresden - Technische Universität Dresden = Dresden University of Technology
2 Aston University [Birmingham]
3 Mécanismes moléculaires du transport intracellulaire
4 PICT-IBiSA - BioImaging Cell and Tissue Core Facility

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.

Domaines: Biologie cellulaire; Biochimie, Biologie Moléculaire

Sofia Traikov, Christoph Stange, Thomas Wassmer, Perrine Paul-Gilloteaux, Jean Salamero, et al.. Septin6 and Septin7 GTP Binding Proteins Regulate AP-3- and ESCRT-Dependent Multivesicular Body Biogenesis. PLoS ONE, 2014, 9 (11), pp.e109372. ⟨10.1371/journal.pone.0109372⟩. ⟨hal-01712221⟩