Small GTPases and phosphoinositides in the regulatory mechanisms of macropinosome formation and maturation
Macropinosome formation requires the sequential activation of numerous signaling pathways that coordinate the actin-driven formation of plasma membrane protrusions (ruffles) and circular ruffles (macropinocytic cups), followed by the closure of these macropinocytic cups into macropinosomes. In the p...
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Frontiers Media S.A.
2014-09-01
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Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00374/full |
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author | Youhei eEgami Tomohiko eTaguchi Tomohiko eTaguchi Masashi eMaekawa Masashi eMaekawa Hiroyuki eArai Hiroyuki eArai Nobukazu eAraki |
author_facet | Youhei eEgami Tomohiko eTaguchi Tomohiko eTaguchi Masashi eMaekawa Masashi eMaekawa Hiroyuki eArai Hiroyuki eArai Nobukazu eAraki |
author_sort | Youhei eEgami |
collection | DOAJ |
description | Macropinosome formation requires the sequential activation of numerous signaling pathways that coordinate the actin-driven formation of plasma membrane protrusions (ruffles) and circular ruffles (macropinocytic cups), followed by the closure of these macropinocytic cups into macropinosomes. In the process of macropinosome formation, localized productions of phosphoinositides such as PI(4,5)P2 and PI(3,4,5)P3 spatiotemporally orchestrate actin polymerization and rearrangement through recruiting and activating a variety of actin-associated proteins. In addition, the sequential activation of small GTPases, which are known to be master regulators of the actin cytoskeleton, plays a pivotal role in parallel with phosphoinositides. To complete macropinosome formation, phosphoinositide breakdown and Rho GTPase deactivation must occur in appropriate timings. After the nascent macropinosomes are formed, phosphoinositides and several Rab GTPases control macropinosome maturation by regulating vesicle trafficking and membrane fusion. In this review, we summarize recent advances in our understanding of the critical functions of phosphoinositide metabolism and small GTPases in association with their downstream effectors in macropinocytosis. |
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id | doaj.art-976c4c4d8693495cba963732c6b792f9 |
institution | Directory Open Access Journal |
issn | 1664-042X |
language | English |
last_indexed | 2024-12-14T09:23:17Z |
publishDate | 2014-09-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Physiology |
spelling | doaj.art-976c4c4d8693495cba963732c6b792f92022-12-21T23:08:15ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2014-09-01510.3389/fphys.2014.00374110361Small GTPases and phosphoinositides in the regulatory mechanisms of macropinosome formation and maturationYouhei eEgami0Tomohiko eTaguchi1Tomohiko eTaguchi2Masashi eMaekawa3Masashi eMaekawa4Hiroyuki eArai5Hiroyuki eArai6Nobukazu eAraki7Kagawa University School of MedicineGraduate School of Pharmaceutical Sciences, University of TokyoGraduate School of Pharmaceutical Sciences, University of TokyoGraduate School of Pharmaceutical Sciences, University of TokyoLi Ka Shing Knowledge Institute, St. Michael’s HospitalGraduate School of Pharmaceutical Sciences, University of TokyoGraduate School of Pharmaceutical Sciences, University of TokyoKagawa University School of MedicineMacropinosome formation requires the sequential activation of numerous signaling pathways that coordinate the actin-driven formation of plasma membrane protrusions (ruffles) and circular ruffles (macropinocytic cups), followed by the closure of these macropinocytic cups into macropinosomes. In the process of macropinosome formation, localized productions of phosphoinositides such as PI(4,5)P2 and PI(3,4,5)P3 spatiotemporally orchestrate actin polymerization and rearrangement through recruiting and activating a variety of actin-associated proteins. In addition, the sequential activation of small GTPases, which are known to be master regulators of the actin cytoskeleton, plays a pivotal role in parallel with phosphoinositides. To complete macropinosome formation, phosphoinositide breakdown and Rho GTPase deactivation must occur in appropriate timings. After the nascent macropinosomes are formed, phosphoinositides and several Rab GTPases control macropinosome maturation by regulating vesicle trafficking and membrane fusion. In this review, we summarize recent advances in our understanding of the critical functions of phosphoinositide metabolism and small GTPases in association with their downstream effectors in macropinocytosis.http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00374/fullphosphoinositidesRac1optogeneticssmall GTPasesmacropinocytosisMyotubularin-related proteins |
spellingShingle | Youhei eEgami Tomohiko eTaguchi Tomohiko eTaguchi Masashi eMaekawa Masashi eMaekawa Hiroyuki eArai Hiroyuki eArai Nobukazu eAraki Small GTPases and phosphoinositides in the regulatory mechanisms of macropinosome formation and maturation Frontiers in Physiology phosphoinositides Rac1 optogenetics small GTPases macropinocytosis Myotubularin-related proteins |
title | Small GTPases and phosphoinositides in the regulatory mechanisms of macropinosome formation and maturation |
title_full | Small GTPases and phosphoinositides in the regulatory mechanisms of macropinosome formation and maturation |
title_fullStr | Small GTPases and phosphoinositides in the regulatory mechanisms of macropinosome formation and maturation |
title_full_unstemmed | Small GTPases and phosphoinositides in the regulatory mechanisms of macropinosome formation and maturation |
title_short | Small GTPases and phosphoinositides in the regulatory mechanisms of macropinosome formation and maturation |
title_sort | small gtpases and phosphoinositides in the regulatory mechanisms of macropinosome formation and maturation |
topic | phosphoinositides Rac1 optogenetics small GTPases macropinocytosis Myotubularin-related proteins |
url | http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00374/full |
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