Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation. / Steffen, Anika; Ladwein, Markus; Dimchev, Georgi A; Hein, Anke; Schwenkmezger, Lisa; Arens, Stefan; Ladwein, Kathrin I; Margit Holleboom, J; Schur, Florian; Victor Small, J; Schwarz, Janett; Gerhard, Ralf; Faix, Jan; Stradal, Theresia E B; Brakebusch, Cord Herbert; Rottner, Klemens.
In: Journal of Cell Science, Vol. 126, No. Pt 20, 15.10.2013, p. 4572-88.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation
AU - Steffen, Anika
AU - Ladwein, Markus
AU - Dimchev, Georgi A
AU - Hein, Anke
AU - Schwenkmezger, Lisa
AU - Arens, Stefan
AU - Ladwein, Kathrin I
AU - Margit Holleboom, J
AU - Schur, Florian
AU - Victor Small, J
AU - Schwarz, Janett
AU - Gerhard, Ralf
AU - Faix, Jan
AU - Stradal, Theresia E B
AU - Brakebusch, Cord Herbert
AU - Rottner, Klemens
PY - 2013/10/15
Y1 - 2013/10/15
N2 - 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 also by RhoG or Cdc42. Here we describe viable fibroblast cell lines genetically deficient 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.
AB - 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 also by RhoG or Cdc42. Here we describe viable fibroblast cell lines genetically deficient 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.
U2 - 10.1242/jcs.118232
DO - 10.1242/jcs.118232
M3 - Journal article
C2 - 23902686
VL - 126
SP - 4572
EP - 4588
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - Pt 20
ER -
ID: 108162554