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Published online 11 February 2002. doi:10.1083/jcb.200106008
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© The Rockefeller University Press, 0021-9525/2002/2/737 $5.00
The Journal of Cell Biology, Volume 156, Number 4, February 18, 2002 737-750

Article

 Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells

Gerhard Schratt1, Ulrike Philippar1, Jürgen Berger2, Heinz Schwarz2, Olaf Heidenreich1 and Alfred Nordheim1

1 Interfakultäres Institut für Zellbiologie, Abteilung Molekularbiologie, Universität Tübingen, 72076 Tübingen, Germany
2 Max-Planck-Institut für Entwicklungsbiologie, 72076 Tübingen, Germany

Address correspondence to Alfred Nordheim, Interfakultäres Institut für Zellbiologie, Abteilung Molekularbiologie, Universität Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany. Tel.: (49) 7071-2978898. Fax: (49) 7071-295359. E-mail: alfred.nordheim{at}uni-tuebingen.de

The activity of serum response factor (SRF), an essential transcription factor in mouse gastrulation, is regulated by changes in actin dynamics. Using Srf(-/-) embryonic stem (ES) cells, we demonstrate that SRF deficiency causes impairments in ES cell spreading, adhesion, and migration. These defects correlate with defective formation of cytoskeletal structures, namely actin stress fibers and focal adhesion (FA) plaques. The FA proteins FA kinase (FAK), ß1-integrin, talin, zyxin, and vinculin were downregulated and/or mislocalized in ES cells lacking SRF, leading to inefficient activation of the FA signaling kinase FAK. Reduced overall actin expression levels in Srf(-/-) ES cells were accompanied by an offset treadmilling equilibrium, resulting in lowered F-actin levels. Expression of active RhoA-V14 rescued F-actin synthesis but not stress fiber formation. Introduction of constitutively active SRF-VP16 into Srf(-/-) ES cells, on the other hand, strongly induced expression of FA components and F-actin synthesis, leading to a dramatic reorganization of actin filaments into stress fibers and lamellipodia. Thus, using ES cell genetics, we demonstrate for the first time the importance of SRF for the formation of actin-directed cytoskeletal structures that determine cell spreading, adhesion, and migration. Our findings suggest an involvement of SRF in cell migratory processes in multicellular organisms.

Key Words: SRF; ES cells; actin cytoskeleton; focal adhesion; cell migration


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