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

Lookup NU author(s): Professor Olaf Heidenreich

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Abstract

The activity of serum response factor (SRF), an essential transcription factor in mouse gastrulation, is regulated by changes in actin dynamics. Using Srf([minus sign]/[minus sign]) 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), [beta]1-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([minus sign]/[minus sign]) 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([minus sign]/[minus sign]) 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.

Publication metadata

Author(s): Schratt G, Philippar U, Berger J, Schwarz H, Heidenreich O, Nordheim A

Publication type: Article

Publication status: Published

Journal: Journal of Cellular Biology

Year: 2002

Volume: 156

Issue: 4

Pages: 737-750

ISSN (print): 0021-9525

ISSN (electronic): 1540-8140

URL: http://dx.doi.org/10.1083/jcb.200106008

DOI: 10.1083/jcb.200106008

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