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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
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The PIKfyve complex regulates the early melanosome homeostasis required for physiological amyloid formation

Christin Bissig1, Pauline Croisé2, Xavier Heiligenstein1,3

  • 1Structure and Membrane Compartments, Institut Curie, Paris Sciences & Lettres Research University, Centre National de la Recherche Scientifique, UMR144, 75005 Paris, France.

Journal of Cell Science
|February 3, 2019
PubMed

Insights

PIKfyve enzyme activity is crucial for melanosome identity and function. It regulates the formation of amyloid matrix within melanosomes, essential for pigment production and cell health.

Area of Science:

  • Cell Biology
  • Melanogenesis
  • Biochemistry

Background:

  • The PIKfyve, VAC14, and FIG4 complex regulates PI(3,5)P2 metabolism.
  • Mutations in this complex cause hypopigmentation, suggesting a role in melanosome biogenesis.
  • The precise function of this complex in melanocytes remains largely unexplored.

Purpose of the Study:

  • To investigate the role of PIKfyve activity in melanosome biogenesis.
  • To elucidate the molecular mechanisms by which PIKfyve influences melanosome identity and function.

Main Methods:

  • Utilized melanocyte cell models.
  • Investigated the impact of PIKfyve activity on melanosome structure and protein processing.
  • Examined interactions between melanosomes and lysosomes.

Main Results:

  • PIKfyve activity is essential for forming the PMEL protein amyloid matrix in stage I melanosomes.
  • PIKfyve regulates membrane remodeling, PMEL protein abundance, sorting, and processing.
  • PIKfyve modulates lysosome-melanosome kiss-and-run interactions, crucial for amyloidogenesis and melanosome identity.
  • PIKfyve influences endosomal actin branching, affecting membrane tubule formation and release from stage I melanosomes.

Conclusions:

  • PIKfyve activity is a key regulator of melanosomal import-export machinery.
  • PIKfyve fine-tunes the formation of functional amyloid fibrils and maintains melanosome identity.
  • This study highlights a novel role for PIKfyve in pigment production and cellular homeostasis.
Keywords:
AmyloidFIG4LysosomeMelanosomePI(3,5)P2PIKfyvePMELPhosphoinositideVAC14

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