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Type II phosphatidylinositol 4-kinases function sequentially in cargo delivery from early endosomes to melanosomes. | LitMetric

AI Article Synopsis

  • * The maturation process involves BLOC-1, which is essential for forming tubular transport carriers that deliver necessary materials to melanosomes, and relies on phosphatidylinositol-4-phosphate and two kinases (PI4KIIα and PI4KIIβ).
  • * Research shows that both PI4KIIα and PI4KIIβ play crucial roles in the elongation of these tubular carriers and the successful delivery of melanin components, indicating they are needed for proper melanosome function and biogenesis.

Article Abstract

Melanosomes are pigment cell-specific lysosome-related organelles in which melanin pigments are synthesized and stored. Melanosome maturation requires delivery of melanogenic cargoes via tubular transport carriers that emanate from early endosomes and that require BLOC-1 for their formation. Here we show that phosphatidylinositol-4-phosphate (PtdIns4P) and the type II PtdIns-4-kinases (PI4KIIα and PI4KIIβ) support BLOC-1-dependent tubule formation to regulate melanosome biogenesis. Depletion of either PI4KIIα or PI4KIIβ with shRNAs in melanocytes reduced melanin content and misrouted BLOC-1-dependent cargoes to late endosomes/lysosomes. Genetic epistasis, cell fractionation, and quantitative live-cell imaging analyses show that PI4KIIα and PI4KIIβ function sequentially and non-redundantly downstream of BLOC-1 during tubule elongation toward melanosomes by generating local pools of PtdIns4P. The data show that both type II PtdIns-4-kinases are necessary for efficient BLOC-1-dependent tubule elongation and subsequent melanosome contact and content delivery during melanosome biogenesis. The independent functions of PtdIns-4-kinases in tubule extension are downstream of likely redundant functions in BLOC-1-dependent tubule initiation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524207PMC
http://dx.doi.org/10.1083/jcb.202110114DOI Listing

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