A dynamin-cortactin-Arp2/3 complex mediates actin reorganization in growth factor-stimulated cells

Eugene W. Krueger, James D. Orth, Hong Cao, Mark A Mc Niven

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

The mechanisms by which mammalian cells remodel the actin cytoskeleton in response to motogenic stimuli are complex and a topic of intense study. Dynamin 2 (Dyn2) is a large GTPase that interacts directly with several actin binding proteins, including cortactin. In this study, we demonstrate that Dyn2 and cortactin function to mediate dynamic remodeling of the actin cytoskeleton in response to stimulation with the motogenic growth factor platelet-derived growth factor. On stimulation, Dyn2 and cortactin coassemble into large, circular structures on the dorsal cell surface. These "waves" promote an active reorganization of actin filaments in the anterior cytoplasm and function to disassemble actin stress fibers. Importantly, inhibition of Dyn2 and cortactin function potently blocked the formation of waves and subsequent actin reorganization. These findings demonstrate that cortactin and Dyn2 function together in a supramolecular complex that assembles in response to growth factor stimulation and mediates the remodeling of actin to facilitate lamellipodial protrusion at the leading edge of migrating cells.

Original languageEnglish (US)
Pages (from-to)1085-1096
Number of pages12
JournalMolecular Biology of the Cell
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2003

Fingerprint

Dynamin II
Cortactin
Actin-Related Protein 2-3 Complex
Dynamins
Actins
Intercellular Signaling Peptides and Proteins
Actin Cytoskeleton
Microfilament Proteins
Stress Fibers
GTP Phosphohydrolases
Platelet-Derived Growth Factor
Cytoplasm

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

A dynamin-cortactin-Arp2/3 complex mediates actin reorganization in growth factor-stimulated cells. / Krueger, Eugene W.; Orth, James D.; Cao, Hong; Mc Niven, Mark A.

In: Molecular Biology of the Cell, Vol. 14, No. 3, 01.03.2003, p. 1085-1096.

Research output: Contribution to journalArticle

@article{f207f3659e9d42bd8d1260db838b9bb7,
title = "A dynamin-cortactin-Arp2/3 complex mediates actin reorganization in growth factor-stimulated cells",
abstract = "The mechanisms by which mammalian cells remodel the actin cytoskeleton in response to motogenic stimuli are complex and a topic of intense study. Dynamin 2 (Dyn2) is a large GTPase that interacts directly with several actin binding proteins, including cortactin. In this study, we demonstrate that Dyn2 and cortactin function to mediate dynamic remodeling of the actin cytoskeleton in response to stimulation with the motogenic growth factor platelet-derived growth factor. On stimulation, Dyn2 and cortactin coassemble into large, circular structures on the dorsal cell surface. These {"}waves{"} promote an active reorganization of actin filaments in the anterior cytoplasm and function to disassemble actin stress fibers. Importantly, inhibition of Dyn2 and cortactin function potently blocked the formation of waves and subsequent actin reorganization. These findings demonstrate that cortactin and Dyn2 function together in a supramolecular complex that assembles in response to growth factor stimulation and mediates the remodeling of actin to facilitate lamellipodial protrusion at the leading edge of migrating cells.",
author = "Krueger, {Eugene W.} and Orth, {James D.} and Hong Cao and {Mc Niven}, {Mark A}",
year = "2003",
month = "3",
day = "1",
doi = "10.1091/mbc.E02-08-0466",
language = "English (US)",
volume = "14",
pages = "1085--1096",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "3",

}

TY - JOUR

T1 - A dynamin-cortactin-Arp2/3 complex mediates actin reorganization in growth factor-stimulated cells

AU - Krueger, Eugene W.

AU - Orth, James D.

AU - Cao, Hong

AU - Mc Niven, Mark A

PY - 2003/3/1

Y1 - 2003/3/1

N2 - The mechanisms by which mammalian cells remodel the actin cytoskeleton in response to motogenic stimuli are complex and a topic of intense study. Dynamin 2 (Dyn2) is a large GTPase that interacts directly with several actin binding proteins, including cortactin. In this study, we demonstrate that Dyn2 and cortactin function to mediate dynamic remodeling of the actin cytoskeleton in response to stimulation with the motogenic growth factor platelet-derived growth factor. On stimulation, Dyn2 and cortactin coassemble into large, circular structures on the dorsal cell surface. These "waves" promote an active reorganization of actin filaments in the anterior cytoplasm and function to disassemble actin stress fibers. Importantly, inhibition of Dyn2 and cortactin function potently blocked the formation of waves and subsequent actin reorganization. These findings demonstrate that cortactin and Dyn2 function together in a supramolecular complex that assembles in response to growth factor stimulation and mediates the remodeling of actin to facilitate lamellipodial protrusion at the leading edge of migrating cells.

AB - The mechanisms by which mammalian cells remodel the actin cytoskeleton in response to motogenic stimuli are complex and a topic of intense study. Dynamin 2 (Dyn2) is a large GTPase that interacts directly with several actin binding proteins, including cortactin. In this study, we demonstrate that Dyn2 and cortactin function to mediate dynamic remodeling of the actin cytoskeleton in response to stimulation with the motogenic growth factor platelet-derived growth factor. On stimulation, Dyn2 and cortactin coassemble into large, circular structures on the dorsal cell surface. These "waves" promote an active reorganization of actin filaments in the anterior cytoplasm and function to disassemble actin stress fibers. Importantly, inhibition of Dyn2 and cortactin function potently blocked the formation of waves and subsequent actin reorganization. These findings demonstrate that cortactin and Dyn2 function together in a supramolecular complex that assembles in response to growth factor stimulation and mediates the remodeling of actin to facilitate lamellipodial protrusion at the leading edge of migrating cells.

UR - http://www.scopus.com/inward/record.url?scp=0037343053&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037343053&partnerID=8YFLogxK

U2 - 10.1091/mbc.E02-08-0466

DO - 10.1091/mbc.E02-08-0466

M3 - Article

VL - 14

SP - 1085

EP - 1096

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 3

ER -