PIKfyve regulates melanosome biogenesis

PLoS Genet. 2018 Mar 27;14(3):e1007290. doi: 10.1371/journal.pgen.1007290. eCollection 2018 Mar.

Abstract

PIKfyve, VAC14, and FIG4 form a complex that catalyzes the production of PI(3,5)P2, a signaling lipid implicated in process ranging from lysosome maturation to neurodegeneration. While previous studies have identified VAC14 and FIG4 mutations that lead to both neurodegeneration and coat color defects, how PIKfyve regulates melanogenesis is unknown. In this study, we sought to better understand the role of PIKfyve in melanosome biogenesis. Melanocyte-specific PIKfyve knockout mice exhibit greying of the mouse coat and the accumulation of single membrane vesicle structures in melanocytes resembling multivesicular endosomes. PIKfyve inhibition blocks melanosome maturation, the processing of the melanosome protein PMEL, and the trafficking of the melanosome protein TYRP1. Taken together, these studies identify a novel role for PIKfyve in controlling the delivery of proteins from the endosomal compartment to the melanosome, a role that is distinct from the role of PIKfyve in the reformation of lysosomes from endolysosomes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Flavoproteins / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Melanins / metabolism
  • Melanosomes / metabolism*
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Organelles / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphoinositide Phosphatases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Protein Transport

Substances

  • Flavoproteins
  • Intracellular Signaling Peptides and Proteins
  • Melanins
  • Membrane Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Vac14 protein, mouse
  • Pikfyve protein, mouse
  • Fig4 protein, mouse
  • Phosphoinositide Phosphatases