The PIKfyve complex regulates the early melanosome homeostasis required for physiological amyloid formation.
Amyloid
/ metabolism
Animals
Cells, Cultured
Flavoproteins
/ genetics
Homeostasis
Intracellular Signaling Peptides and Proteins
/ genetics
Lysosomes
/ metabolism
Melanocytes
/ metabolism
Melanosomes
/ metabolism
Membrane Proteins
/ genetics
Mice
Mice, Knockout
Phosphatidylinositol 3-Kinases
/ genetics
Phosphoinositide Phosphatases
/ genetics
Protein Transport
Retinal Pigment Epithelium
/ metabolism
gp100 Melanoma Antigen
/ metabolism
Amyloid
FIG4
Lysosome
Melanosome
PI(3,5)P2
PIKfyve
PMEL
Phosphoinositide
VAC14
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
28 02 2019
28 02 2019
Historique:
received:
03
01
2019
accepted:
14
01
2019
pubmed:
3
2
2019
medline:
2
6
2020
entrez:
3
2
2019
Statut:
epublish
Résumé
The metabolism of PI(3,5)P2 is regulated by the PIKfyve, VAC14 and FIG4 complex, mutations in which are associated with hypopigmentation in mice. These pigmentation defects indicate a key, but as yet unexplored, physiological relevance of this complex in the biogenesis of melanosomes. Here, we show that PIKfyve activity regulates formation of amyloid matrix composed of PMEL protein within the early endosomes in melanocytes, called stage I melanosomes. PIKfyve activity controls the membrane remodeling of stage I melanosomes, which regulates PMEL abundance, sorting and processing. PIKfyve activity also affects stage I melanosome kiss-and-run interactions with lysosomes, which are required for PMEL amyloidogenesis and the establishment of melanosome identity. Mechanistically, PIKfyve activity promotes both the formation of membrane tubules from stage I melanosomes and their release by modulating endosomal actin branching. Taken together, our data indicate that PIKfyve activity is a key regulator of the melanosomal import-export machinery that fine tunes the formation of functional amyloid fibrils in melanosomes and the maintenance of melanosome identity.This article has an associated First Person interview with the first author of the paper.
Identifiants
pubmed: 30709920
pii: jcs.229500
doi: 10.1242/jcs.229500
pmc: PMC6432708
pii:
doi:
Substances chimiques
Amyloid
0
Flavoproteins
0
Intracellular Signaling Peptides and Proteins
0
Membrane Proteins
0
Pmel protein, mouse
0
Vac14 protein, mouse
0
gp100 Melanoma Antigen
0
Pikfyve protein, mouse
EC 2.7.1.137
Fig4 protein, mouse
EC 3.1.3.36
Phosphoinositide Phosphatases
EC 3.1.3.36
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM024872
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS064015
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS099340
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2019. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.
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