Type II phosphatidylinositol 4-kinases function sequentially in cargo delivery from early endosomes to melanosomes.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
07 11 2022
07 11 2022
Historique:
received:
20
10
2021
revised:
31
03
2022
accepted:
04
05
2022
entrez:
28
9
2022
pubmed:
29
9
2022
medline:
1
10
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36169639
pii: 213509
doi: 10.1083/jcb.202110114
pmc: PMC9524207
pii:
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
Melanins
0
Phosphatidylinositol Phosphates
0
phosphatidylinositol 4-phosphate
0
1-Phosphatidylinositol 4-Kinase
EC 2.7.1.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Centre National de la Recherche Scientifique
Organisme : Genespoir
Organisme : Institut Curie
Organisme : NEI NIH HHS
ID : R01 EY015625
Pays : United States
Organisme : Institut National de la Santé et de la Recherche Médicale
Informations de copyright
© 2022 Zhu et al.
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