Nucleoskeletal regulation of transcription: Actin on MRTF

Abstract

Myocardin-related transcription factor A (MRTF-A) and serum response factor (SRF) form an essential transcriptional complex that regulates the expression of many cytoskeletal genes in response to dynamic changes in the actin cytoskeleton. The nucleoskeleton, a “dynamic network of networks,” consists of numerous proteins that contribute to nuclear shape and to its various functions, including gene expression. In this review, we will discuss recent work that has identified many nucleoskeletal proteins, such as nuclear lamina and lamina-associated proteins, nuclear actin, and the linker of the cytoskeleton and nucleoskeleton complex as important regulators of MRTF-A/SRF transcriptional activity, especially in the context of mechanical control of transcription.

Impact statement: Regulation of gene expression is a fundamental cellular process that ensures the appropriate response of a cell to its surroundings. Alongside biochemical signals, mechanical cues, such as substrate rigidity, have been recognized as key regulators of gene expression. Nucleoskeletal components play an important role in mechanoresponsive transcription, particularly in controlling the activity of MRTF-A/SRF transcription factors. This ensures that the cell can balance the internal and external mechanical forces by fine-tuning the expression of cytoskeletal genes.

Keywords: Actin; myocardin-related transcription factor; nucleoskeleton; serum response factor nuclear lamina; transcription.

Figure 1.

Schematic model of MRTF-A/SRF complex regulation by nucleoskeletal components. (a) Regulation via nuclear actin polymerization and stabilization of filaments. (I) LINC complex mediates cell spreading-induced signaling from integrins to nuclear formins mDia that promote nuclear actin polymerization. (II) Inner nuclear membrane protein emerin facilitates polymerization of nuclear actin via an unknown mechanism. (III) Filamin A (FLNA) facilitates nuclear actin polymerization and links the filaments to MRTF-A/SRF complex. (b) Regulation of RhoA and MRTF-A/SRF activity by LINC complex. SUN2 LINC complexes signal from the nuclear envelope through the cytoplasm to increase the pool of active RhoA and consequently promote MRTF-A/SRF complex activation. SUN1 complexes antagonize this network. (A color version of this figure is available in the online journal.)