The phosphoinositide coincidence detector Phafin2 promotes macropinocytosis by coordinating actin organisation at forming macropinosomes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 11 2021
12 11 2021
Historique:
received:
05
07
2021
accepted:
08
10
2021
entrez:
13
11
2021
pubmed:
14
11
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Uptake of large volumes of extracellular fluid by actin-dependent macropinocytosis has an important role in infection, immunity and cancer development. A key question is how actin assembly and disassembly are coordinated around macropinosomes to allow them to form and subsequently pass through the dense actin network underlying the plasma membrane to move towards the cell center for maturation. Here we show that the PH and FYVE domain protein Phafin2 is recruited transiently to newly-formed macropinosomes by a mechanism that involves coincidence detection of PtdIns3P and PtdIns4P. Phafin2 also interacts with actin via its PH domain, and recruitment of Phafin2 coincides with actin reorganization around nascent macropinosomes. Moreover, forced relocalization of Phafin2 to the plasma membrane causes rearrangement of the subcortical actin cytoskeleton. Depletion of Phafin2 inhibits macropinosome internalization and maturation and prevents KRAS-transformed cancer cells from utilizing extracellular protein as an amino acid source. We conclude that Phafin2 promotes macropinocytosis by controlling timely delamination of actin from nascent macropinosomes for their navigation through the dense subcortical actin network.
Identifiants
pubmed: 34772942
doi: 10.1038/s41467-021-26775-x
pii: 10.1038/s41467-021-26775-x
pmc: PMC8590015
doi:
Substances chimiques
Actins
0
PLEKHF2 protein, human
0
Phosphatidylinositol Phosphates
0
Phosphatidylinositols
0
Vesicular Transport Proteins
0
phosphatidylinositol 3-phosphate
0
phosphatidylinositol 4-phosphate
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6577Informations de copyright
© 2021. The Author(s).
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