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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.

SUBMITTER: Maekawa M

PROVIDER: S-EPMC3964036 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Maekawa Masashi M Terasaka Shimpei S Mochizuki Yasuhiro Y Kawai Katsuhisa K Ikeda Yuka Y Araki Nobukazu N Skolnik Edward Y EY Taguchi Tomohiko T Arai Hiroyuki H

Proceedings of the National Academy of Sciences of the United States of America 20140303 11

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 ...[more]

PMID: 24591580

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Project description:BACKGROUND:Effective strategies for contacting and recruiting study participants are critical in conducting clinical research. In this study, we conducted two sequential randomized controlled trials of mail- and telephone-based strategies for contacting and recruiting participants, and evaluated participant-related variables' association with time to survey completion and survey completion rates. Subjects eligible for this study were survivors of acute lung injury who had been previously enrolled in a 12-month observational follow-up study evaluating their physical, cognitive and mental health outcomes, with their last study visit completed at a median of 34 months previously. METHODS:Eligible subjects were contacted to complete a new research survey as part of two randomized trials, initially using a randomized mail-based contact strategy, followed by a randomized telephone-based contact strategy for non-responders to the mail strategy. Both strategies focused on using either a personalized versus a generic approach. In addition, 18 potentially relevant subject-related variables (e.g., demographics, last known physical and mental health status) were evaluated for association with time to survey completion. RESULTS:Of 308 eligible subjects, 67% completed the survey with a median (IQR) of 3 (2, 5) contact attempts required. There was no significant difference in the time to survey completion for either randomized trial of mail- or phone-based contact strategy. Among all subject-related variables, age ?40 years and minority race were independently associated with a longer time to survey completion. CONCLUSION:We found that age ?40 years and minority race were associated with a longer time to survey completion, but personalized versus generic approaches to mail- and telephone-based contact strategies had no significant effect. Repeating both mail and telephone contact attempts was important for increasing survey completion rate. TRIAL REGISTRATION:NCT00719446.

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

Publications

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

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