---
_id: '811'
abstract:
- lang: eng
text: Cell migration is commonly accompanied by protrusion of membrane ruffles and
lamellipodia. In two-dimensional migration, protrusion of these thin sheets of
cytoplasm is considered relevant to both exploration of new space and initiation
of nascent adhesion to the substratum. Lamellipodium formation can be potently
stimulated by Rho GTPases of the Rac subfamily, but alsoby RhoG or Cdc42. Here
we describe viable fibroblast cell lines geneticallydeficient for Rac1 that lack
detectable levels of Rac2 and Rac3. Rac-deficient cells were devoid of apparent
lamellipodia, but these structures were restored by expression of either Rac subfamily
member, but not by Cdc42 or RhoG. Cells deficient in Rac showed strong reduction
in wound closure and random cell migration and a notable loss of sensitivity to
a chemotactic gradient. Despite these defects, Rac-deficient cells were able to
spread, formed filopodia and established focal adhesions. Spreading in these cells
was achieved by the extension of filopodia followed by the advancement of cytoplasmic
veils between them. The number and size of focal adhesions as well as their intensity
were largely unaffected by genetic removal of Rac1. However, Rac deficiency increased
the mobility of different components in focal adhesions, potentially explaining
how Rac - although not essential - can contribute to focal adhesion assembly.
Together, our data demonstrate that Rac signaling is essential for lamellipodium
protrusion and for efficient cell migration, but not for spreading or filopodium
formation. Our findings also suggest that Rac GTPases are crucial to the establishment
or maintenance of polarity in chemotactic migration.
acknowledgement: |-
This work was supported in part by the Deutsche Forschungsgemeinschaft [grants within programs SFB621 to K.R., and FOR629 and SFB629 to T.E.B.S.]. Deposited in PMC for immediate release.
We thank Brigitte Denker and Gerd Landsberg for excellent technical assistance. We are grateful to Robert Geffers (HZI Braunschweig, Germany) for microarray analyses and to Mirko Himmel (UKE Hamburg, Germany) for valuable advice on FRAP analysis.
author:
- first_name: Anika
full_name: Steffen, Anika
last_name: Steffen
- first_name: Markus
full_name: Ladwein, Markus
last_name: Ladwein
- first_name: Georgi A
full_name: Georgi Dimchev
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
- first_name: Anke
full_name: Hein, Anke
last_name: Hein
- first_name: Lisa
full_name: Schwenkmezger, Lisa
last_name: Schwenkmezger
- first_name: Stefan
full_name: Arens, Stefan
last_name: Arens
- first_name: Kathrin
full_name: Ladwein, Kathrin I
last_name: Ladwein
- first_name: J.
full_name: Holleboom, J. Margit
last_name: Holleboom
- first_name: Florian
full_name: Florian Schur
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: John
full_name: Small, John V
last_name: Small
- first_name: Janett
full_name: Schwarz, Janett
last_name: Schwarz
- first_name: Ralf
full_name: Gerhard, Ralf
last_name: Gerhard
- first_name: Jan
full_name: Faix, Jan
last_name: Faix
- first_name: Theresia
full_name: Stradal, Theresia E
last_name: Stradal
- first_name: Cord
full_name: Brakebusch, Cord H
last_name: Brakebusch
- first_name: Klemens
full_name: Rottner, Klemens
last_name: Rottner
citation:
ama: Steffen A, Ladwein M, Dimchev GA, et al. Rac function is crucial for cell migration
but is not required for spreading and focal adhesion formation. Journal of
Cell Science. 2013;126(20):4572-4588. doi:10.1242/jcs.118232
apa: Steffen, A., Ladwein, M., Dimchev, G. A., Hein, A., Schwenkmezger, L., Arens,
S., … Rottner, K. (2013). Rac function is crucial for cell migration but is not
required for spreading and focal adhesion formation. Journal of Cell Science.
Company of Biologists. https://doi.org/10.1242/jcs.118232
chicago: Steffen, Anika, Markus Ladwein, Georgi A Dimchev, Anke Hein, Lisa Schwenkmezger,
Stefan Arens, Kathrin Ladwein, et al. “Rac Function Is Crucial for Cell Migration
but Is Not Required for Spreading and Focal Adhesion Formation.” Journal of
Cell Science. Company of Biologists, 2013. https://doi.org/10.1242/jcs.118232.
ieee: A. Steffen et al., “Rac function is crucial for cell migration but
is not required for spreading and focal adhesion formation,” Journal of Cell
Science, vol. 126, no. 20. Company of Biologists, pp. 4572–4588, 2013.
ista: Steffen A, Ladwein M, Dimchev GA, Hein A, Schwenkmezger L, Arens S, Ladwein
K, Holleboom J, Schur FK, Small J, Schwarz J, Gerhard R, Faix J, Stradal T, Brakebusch
C, Rottner K. 2013. Rac function is crucial for cell migration but is not required
for spreading and focal adhesion formation. Journal of Cell Science. 126(20),
4572–4588.
mla: Steffen, Anika, et al. “Rac Function Is Crucial for Cell Migration but Is Not
Required for Spreading and Focal Adhesion Formation.” Journal of Cell Science,
vol. 126, no. 20, Company of Biologists, 2013, pp. 4572–88, doi:10.1242/jcs.118232.
short: A. Steffen, M. Ladwein, G.A. Dimchev, A. Hein, L. Schwenkmezger, S. Arens,
K. Ladwein, J. Holleboom, F.K. Schur, J. Small, J. Schwarz, R. Gerhard, J. Faix,
T. Stradal, C. Brakebusch, K. Rottner, Journal of Cell Science 126 (2013) 4572–4588.
date_created: 2018-12-11T11:48:38Z
date_published: 2013-01-01T00:00:00Z
date_updated: 2021-01-12T08:16:57Z
day: '01'
doi: 10.1242/jcs.118232
extern: 1
intvolume: ' 126'
issue: '20'
month: '01'
page: 4572 - 4588
publication: Journal of Cell Science
publication_status: published
publisher: Company of Biologists
publist_id: '6840'
quality_controlled: 0
status: public
title: Rac function is crucial for cell migration but is not required for spreading
and focal adhesion formation
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
volume: 126
year: '2013'
...