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. Author manuscript; available in PMC: 2011 Apr 11.
Published in final edited form as: Nat Rev Mol Cell Biol. 2010 May;11(5):353–365. doi: 10.1038/nrm2890

Figure 1. receptors affecting actin dynamics and MrTF-mediated regulation of SrF target genes.

Figure 1

a | Cytoskeletal actin microfilament dynamics are affected by the activation of six classes of plasma membrane receptor: receptor Tyr kinases (RTKs), G protein-coupled receptors (GPCRs; with α-subunits of Gα12/13, Gαq/11 or Gαi/0), integrins as structural mediators of focal adhesions, transforming growth factor-β receptors (TGFβRs), E-cadherins at adherens junctions and Frizzled, which mediates the non-canonical Wnt–planar cell polarity (PCP) pathway involving Dishevelled (DVL). These receptors modulate the activity of Rho GTPases2 through Rho guanine nucleotide exchange factors (GEFs). Effectors of Rho GTPases, including Rho-associated kinases (ROCKs), formins (such as Diaphanous-related formins (DRFs)), Wiskott–Aldrich syndrome protein (WASP), WASP-family verprolin homologues (WAVEs) and the actin-related protein 2/3 (ARP2/3) complex and other actin-binding proteins (ABPs), orchestrate actin polymerization by incorporating globular actin (G-actin) into the filamentous actin (F-actin) polymer3. High levels of cytoplasmic G-actin retain serum response factor (SRF) cofactor proteins, myocardin-related transcription factors (MRTFs), in the cytoplasm. Incorporation of G-actin into the F-actin filament liberates MRTFs to enter the nucleus and interact with the transcription factor SRF58. This triggers expression of a subset of SRF target genes, namely cytoskeletal genes. b | Activation of SRF class II target genes. Nuclear MRTF can be complexed by nuclear G-actin, which inhibits MRTF-mediated stimulation of SRF-dependent transcription and facilitates MRTF nuclear export76. SRF class II target genes that are transcribed as a result of MRTF–SRF activation include actin itself and many genes that modulate actin dynamics, such as gelsolin and vinculin. These newly made proteins, with increasing time and concentration, might stimulate cytoplasmic actin polymerization, complex cytoplasmic MRTF or elevate levels of nuclear G-actin to downregulate MRTF-mediated transcription and stimulate nuclear export of MRTF. FAK, focal adhesion kinase; ILK, integrin-linked protein kinase; LIMK, LIM domain kinase.