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Curr Biol. 2016 Jan 11;26(1):1-13. doi: 10.1016/j.cub.2015.11.020. Epub 2015 Dec 24.

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

Author information

1
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.
2
Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, 75005 Paris, France.
3
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.
4
Department of Cell Biology and the Center for Social Translational Neuroscience, Emory University, Atlanta, GA 30322, USA.
5
INSERM U1151-CNRS UMR 8253, Institut Necker Enfants-Malades (INEM) Université, Paris Descartes-Sorbonne Paris Cité Paris, 75993 Paris Cedex 14, France.
6
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.

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.

PMID:
26725201
PMCID:
PMC4713302
DOI:
10.1016/j.cub.2015.11.020
[Indexed for MEDLINE]
Free PMC Article

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