Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis.

Abstract:

:Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and solutes are internalized into cells. Macropinocytosis starts with the formation of membrane ruffles at the plasma membrane and ends with their closure. The transient and sequential emergence of phosphoinositides PI(3,4,5)P3 and PI(3,4)P2 in the membrane ruffles is essential for macropinocytosis. By making use of information in the Caenorhabditis elegans mutants defective in fluid-phase endocytosis, we found that mammalian phosphoinositide phosphatase MTMR6 that dephosphorylates PI(3)P to PI, and its binding partner MTMR9, are required for macropinocytosis. INPP4B, which dephosphorylates PI(3,4)P2 to PI(3)P, was also found to be essential for macropinocytosis. These phosphatases operate after the formation of membrane ruffles to complete macropinocytosis. Finally, we showed that KCa3.1, a Ca(2+)-activated K(+) channel that is activated by PI(3)P, is required for macropinocytosis. We propose that the sequential breakdown of PI(3,4,5)P3 → PI(3,4)P2 → PI(3)P → PI controls macropinocytosis through specific effectors of the intermediate phosphoinositides.

authors

Maekawa M,Terasaka S,Mochizuki Y,Kawai K,Ikeda Y,Araki N,Skolnik EY,Taguchi T,Arai H

doi

10.1073/pnas.1311029111

subject

Has Abstract

pub_date

2014-03-18 00:00:00

pages

E978-87

issue

11

eissn

0027-8424

issn

1091-6490

pii

1311029111

journal_volume

111

pub_type

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