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PIKfyve regulates melanosome biogenesis

Marc C Liggins1, Jessica L Flesher2, Sohail Jahid3

  • 1Department of Dermatology, University of California, San Diego, San Diego, CA, United States of America.

Plos Genetics
|March 28, 2018
PubMed

Insights

PIKfyve is crucial for melanogenesis, controlling protein delivery to melanosomes. Its absence causes coat greying and affects melanosome maturation and protein transport.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Genetics

Background:

  • PIKfyve, VAC14, and FIG4 form a complex producing PI(3,5)P2, a lipid involved in lysosome maturation and neurodegeneration.
  • Mutations in VAC14 and FIG4 cause neurodegeneration and coat color defects, but PIKfyve's role in melanogenesis is unclear.

Purpose of the Study:

  • To investigate the role of PIKfyve in melanosome biogenesis and melanogenesis.

Main Methods:

  • Generation of melanocyte-specific PIKfyve knockout mice.
  • Analysis of melanosome structure and protein processing in knockout mice.
  • Inhibition of PIKfyve activity in melanocytes.

Main Results:

  • PIKfyve knockout mice displayed coat greying and abnormal vesicle accumulation in melanocytes.
  • PIKfyve inhibition disrupted melanosome maturation, PMEL processing, and TYRP1 trafficking.
  • PIKfyve regulates protein delivery from endosomes to melanosomes.

Conclusions:

  • PIKfyve plays a novel role in melanosome biogenesis by controlling protein transport.
  • This function is distinct from PIKfyve's role in lysosome reformation.

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