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Author Notes:

Corresponding author: Cédric Delevoye, Institut Curie, CNRS-UMR144, 26 Rue d’Ulm, 75248 Paris cedex, Tel: +33156246583; Fax: +33156246421; Email: cedric.delevoye@curie.fr

C.D., G.R., E.M., M.S.M and V.F conceived the projects and wrote the manuscript.

C.D. designed and carried out most of the experiments

X.H., L.R., F.G.M, M.K.D., R.A.L., L.D. and A.G. performed experiments

all authors edited the manuscript.

We are grateful to S. Miserey-Lenkei, JB. Brault, P. Monteiro, P. Chavrier and H. Racine (Institut Curie), E. Dell’Angelica (University of California, USA), A. Gautreau (Gif-sur-Yvette, France), V. Gerke (University of Muenster, Germany) and LY. Jan (UCSF, HHMI, USA) for generous gifts of reagents; G. van Niel and C. Bissig for insightful discussions; R. Basto for critical reading of the manuscript; L. Sengmanivong and V. Fraisier (Spatio Temporal Modeling Imaging and Cellular Dynamics-Institut Curie) for image acquisition and deconvolution; and J. Burkhardt (Children’s Hospital of Philadelphia, PA, USA) for using confocal microscope for image acquisition with mouse melanocytes.

Authors declare no conflict of interest.

Subjects:

Research Funding:

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).

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.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Cell Biology
  • LYSOSOME-RELATED ORGANELLES
  • MELANOSOME BIOGENESIS
  • ELECTRON TOMOGRAPHY
  • COMPLEX-1 BLOC-1
  • ARP2/3 ACTIVATOR
  • WASH COMPLEX
  • ANNEXIN-II
  • MEMBRANE
  • PROTEINS
  • DYNAMICS

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

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Journal Title:

Current Biology

Volume:

Volume 26, Number 1

Publisher:

, Pages 1-13

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2016 Elsevier Ltd. Published by Elsevier Inc.

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