BLOC-1 Brings Together the Actin and Microtubule Cytoskeletons to Generate Recycling Endosomes

• Type of Material: Article
• Authors: Cédric Delevoye, PSL Research University; Xavier Heiligenstein, PSL Research University; Léa Ripoll, PSL Research University; Floriane Gilles-Marsens, PSL Research University; Megan K. Dennis, Children’s Hospital of Philadelphia; Ricardo A. Linares, Children's Hospital of Philadelphia; Laura Derman, PSL Research University; Avanti Gokhale, Emory University; Etienne Morel, Institut Necker Enfants-Malades (INEM) Université; Victor Faundez, Emory University; Michael S. Marks, Children's Hospital of Philadelphia; Graça Raposo, PSL Research University
• Language: English
• Date: 2016-01-11
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier Ltd. Published by Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cub.2015.11.020
• Title of Journal or Parent Work: Current Biology
• ISSN: 0960-9822
• Volume: 26
• Issue: 1
• Start Page: 1
• End Page: 13
• Grant/Funding Information: This work was supported by CNRS, INSERM, Institut Curie, National Institutes of Health grants (GM077569 and NS088503 to V.F.), R01 EY015625 from the National Eye Institute (to M.S.M. and G.R.), R01 AR048155 from NIAMS (to M.S.M.) and F32 AR062476 (to M.K.D), and Fondation pour la Recherche Médicale (FRM grant DEQ20140329491 Team label to G.R.).; The authors greatly acknowledge the Nikon Imaging Center @ Institut Curie-CNRS, and the PICT-IBiSA, member of the France-BioImaging national research infrastructure, supported by the CelTisPhyBio Labex (N° ANR-10-LBX-0038) part of the IDEX PSL (N° ANR-10-IDEX-0001-02 PSL).
• Keywords: ANNEXIN-II; Science & Technology; ELECTRON TOMOGRAPHY; Biochemistry & Molecular Biology; ARP2/3 ACTIVATOR; Cell Biology; PROTEINS; DYNAMICS; COMPLEX-1 BLOC-1; WASH COMPLEX; MELANOSOME BIOGENESIS; Life Sciences & Biomedicine; MEMBRANE; LYSOSOME-RELATED ORGANELLES
• Research Categories: Health Sciences, Pathology; Biology, Cell

Abstract

Recycling endosomes consist of a tubular network that emerges from vacuolar sorting endosomes and diverts cargoes toward the cell surface, the Golgi or lysosome-related organelles. How recycling tubules are formed remains unknown. We show that recycling endosome biogenesis requires the protein complex BLOC-1. Mutations in BLOC-1 subunits underlie an inherited disorder characterized by albinism, the Hermansky-Pudlak Syndrome, and are associated with schizophrenia risk. We show here that BLOC-1 coordinates the kinesin KIF13A-dependent pulling of endosomal tubules along microtubules to the Annexin A2/actin-dependent stabilization and detachment of recycling tubules. These components cooperate to extend, stabilize and form tubular endosomal carriers that function in cargo recycling and in the biogenesis of pigment granules in melanocytic cells. By shaping recycling endosomal tubules, our data reveal that dysfunction of the BLOC-1-KIF13A-Annexin A2 molecular network underlies the pathophysiology of neurological and pigmentary disorders.