title: BLOC-1 Brings Together the Actin and Microtubule Cytoskeletons to Generate Recycling Endosomes.
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.
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, 75005 Paris, France; Institut Curie, PSL Research University, CNRS, UMR144, Cell and Tissue Imaging Facility (PICT-IBiSA), 75005 Paris, France. Electronic address: cedric.delevoye@curie.fr.
authors.forename: Cédric
authors.initials: C
authors.lastname: Delevoye
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, 75005 Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Heiligenstein
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, 75005 Paris, France.
authors.forename: Léa
authors.initials: L
authors.lastname: Ripoll
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, 75005 Paris, France.
authors.forename: Floriane
authors.initials: F
authors.lastname: Gilles-Marsens
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine and Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Megan K
authors.initials: MK
authors.lastname: Dennis
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine and Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Linares
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, 75005 Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Derman
authors.affiliation: Department of Cell Biology and the Center for Social Translational Neuroscience, Emory University, Atlanta, GA 30322, USA.
authors.forename: Avanti
authors.initials: A
authors.lastname: Gokhale
authors.affiliation: INSERM U1151-CNRS UMR 8253, Institut Necker Enfants-Malades (INEM) Université, Paris Descartes-Sorbonne Paris Cité Paris, 75993 Paris Cedex 14, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Morel
authors.affiliation: Department of Cell Biology and the Center for Social Translational Neuroscience, Emory University, Atlanta, GA 30322, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Faundez
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine and Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Marks
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, 75005 Paris, France; Institut Curie, PSL Research University, CNRS, UMR144, Cell and Tissue Imaging Facility (PICT-IBiSA), 75005 Paris, France.
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
mesh_terms: D000199:Actins / Q000378:metabolism*; D017306:Annexin A2 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D021381:Protein Transport
chemical_list: C472822:ANXA2 protein, human; D000199:Actins; D017306:Annexin A2; C104378:BLOC1S1 protein, human; C417670:KIF13A protein, human; D009419:Nerve Tissue Proteins; D016547:Kinesins