Type II phosphatidylinositol 4-kinases function sequentially in cargo delivery from early endosomes to melanosomes - Archive ouverte HAL Access content directly
Journal Articles Journal of Cell Biology Year : 2022

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

, , , , (1) , ,
1
Yueyao Zhu
Shuixing Li
  • Function : Author
Alexa Jaume
  • Function : Author
Riddhi Atul Jani
Cédric Delevoye
Graça Raposo
Michael Marks

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.
Not file

Dates and versions

hal-03811922 , version 1 (12-10-2022)

Identifiers

Cite

Yueyao Zhu, Shuixing Li, Alexa Jaume, Riddhi Atul Jani, Cédric Delevoye, et al.. Type II phosphatidylinositol 4-kinases function sequentially in cargo delivery from early endosomes to melanosomes. Journal of Cell Biology, 2022, 221 (11), ⟨10.1083/jcb.202110114⟩. ⟨hal-03811922⟩
4 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More