2. Academic Validation
  3. PIKfyve regulates melanosome biogenesis

PIKfyve regulates melanosome biogenesis

  • PLoS Genet. 2018 Mar 27;14(3):e1007290. doi: 10.1371/journal.pgen.1007290.
Marc C Liggins 1,  Jessica L Flesher 2,  Sohail Jahid 3,  Priya Vasudeva 3,  Victoria Eby 4,  Shunsuke Takasuga 5,  Junko Sasaki 5,  Takehiko Sasaki 5,  Raymond E Boissy 4,  Anand K Ganesan 2 3
Affiliations

Affiliations

  • 1 Department of Dermatology, University of California, San Diego, San Diego, CA, United States of America.
  • 2 Department of Biological Chemistry, University of California, Irvine, Irvine, CA, United States of America.
  • 3 Department of Dermatology, University of California, Irvine, Irvine, CA, United States of America.
  • 4 Department of Dermatology, University of Cincinnati, Cincinnati, OH, United States of America.
  • 5 Department of Medical Biology, Akita University School of Medicine, Akita, Japan.
PMID: 29584722 DOI: 10.1371/journal.pgen.1007290
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.

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