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...

Full description

Bibliographic Details
Main Authors: Youhei eEgami, Tomohiko eTaguchi, Masashi eMaekawa, Hiroyuki eArai, Nobukazu eAraki
Format: Article
Language:English
Published: Frontiers Media S.A. 2014-09-01
Series:Frontiers in Physiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00374/full
_version_ 1818407152384999424
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.
first_indexed 2024-12-14T09:23:17Z
format Article
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.
record_format Article
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
work_keys_str_mv AT youheieegami smallgtpasesandphosphoinositidesintheregulatorymechanismsofmacropinosomeformationandmaturation
AT tomohikoetaguchi smallgtpasesandphosphoinositidesintheregulatorymechanismsofmacropinosomeformationandmaturation
AT tomohikoetaguchi smallgtpasesandphosphoinositidesintheregulatorymechanismsofmacropinosomeformationandmaturation
AT masashiemaekawa smallgtpasesandphosphoinositidesintheregulatorymechanismsofmacropinosomeformationandmaturation
AT masashiemaekawa smallgtpasesandphosphoinositidesintheregulatorymechanismsofmacropinosomeformationandmaturation
AT hiroyukiearai smallgtpasesandphosphoinositidesintheregulatorymechanismsofmacropinosomeformationandmaturation
AT hiroyukiearai smallgtpasesandphosphoinositidesintheregulatorymechanismsofmacropinosomeformationandmaturation
AT nobukazuearaki smallgtpasesandphosphoinositidesintheregulatorymechanismsofmacropinosomeformationandmaturation