BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery

J Cell Biol. 2015 May 25;209(4):563-77. doi: 10.1083/jcb.201410026.

Abstract

Hermansky-Pudlak syndrome (HPS) is a group of disorders characterized by the malformation of lysosome-related organelles, such as pigment cell melanosomes. Three of nine characterized HPS subtypes result from mutations in subunits of BLOC-2, a protein complex with no known molecular function. In this paper, we exploit melanocytes from mouse HPS models to place BLOC-2 within a cargo transport pathway from recycling endosomal domains to maturing melanosomes. In BLOC-2-deficient melanocytes, the melanosomal protein TYRP1 was largely depleted from pigment granules and underwent accelerated recycling from endosomes to the plasma membrane and to the Golgi. By live-cell imaging, recycling endosomal tubules of wild-type melanocytes made frequent and prolonged contacts with maturing melanosomes; in contrast, tubules from BLOC-2-deficient cells were shorter in length and made fewer, more transient contacts with melanosomes. These results support a model in which BLOC-2 functions to direct recycling endosomal tubular transport intermediates to maturing melanosomes and thereby promote cargo delivery and optimal pigmentation.

Publication types

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

MeSH terms

  • Animals
  • Endocytosis
  • Endosomes / metabolism*
  • Golgi Apparatus / metabolism
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Melanocytes / metabolism
  • Melanosomes / metabolism*
  • Membrane Glycoproteins / metabolism
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oxidoreductases / metabolism
  • Protein Transport
  • Skin Pigmentation
  • Vesicular Transport Proteins / physiology*

Substances

  • Hps6 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Vesicular Transport Proteins
  • Oxidoreductases
  • Tyrp1 protein, mouse