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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Annexin A2 / metabolism
  • Cell Membrane / metabolism
  • Endosomes / metabolism*
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Kinesins / metabolism
  • Lysosomes / metabolism
  • Melanocytes / metabolism
  • Microtubules / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Protein Transport


  • ANXA2 protein, human
  • Actins
  • Annexin A2
  • BLOC1S1 protein, human
  • KIF13A protein, human
  • Nerve Tissue Proteins
  • Kinesins