Reorganization of the actin cytoskeleton via transcriptional regulation of cytoskeletal/focal adhesion genes by myocardin-related transcription factors (MRTFs/MAL/MKLs)

Morita, Tsuyoshi; Mayanagi, Taira; Sobue, Kenji

doi:10.1016/j.yexcr.2007.07.008

Cited by 64 publications

(84 citation statements)

References 33 publications

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“…4, A and B). We previously reported that the CALD1 gene is transactivated by the myocardin or myocardin-related transcription factor (MRTF)/SRF pathway in SMCs and fibroblasts (29,31). However, depletion of SRF did not alter the DEX-induced up-regulation of CaD in A549 cells (Fig.…”

Section: Glucocorticoids Suppress Cell Migration and Reorganize The Amentioning

confidence: 86%

“…The SMC-specific transcription of the CALD1 gene is regulated by the coordination of a transcriptional triad composed of the SRF and Nkx homeobox and GATA transcription factors (30). Myocardin is a recently identified co-factor for SRF-mediated transcription of the cardiac and smooth muscle-restricted genes (49), and the Rho-MRTFs-SRF pathway in normal fibroblasts transactivates the actin cytoskeletal genes, including the CALD1 gene (31,50). GR-and SRF-knockdown experiments show that the GC-induced CaD expression solely depends on GR but not on SRF (Figs.…”

Section: Discussionmentioning

confidence: 97%

“…The reporter construct for the fibroblast-type promoter region of the human CALD1 gene was described previously (31). For the mutant constructs, several substitutions were introduced into the two GRE-like sequences in the fibroblast-type promoter as follows: for GRE-like 1, TGT-TCACTTAGCATGGA3 TTTTAACTTAACATGGA; for GRE-like 2, AGAGCAGTGTGTATTC3 AAAGAAGTGT-ATATTC.…”

Section: Methodsmentioning

confidence: 99%

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Glucocorticoid Receptor-mediated Expression of Caldesmon Regulates Cell Migration via the Reorganization of the Actin Cytoskeleton

Mayanagi¹,

Morita

Hayashi

et al. 2008

Journal of Biological Chemistry

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Glucocorticoids (GCs) play important roles in numerous cellular processes, including growth, development, homeostasis, inhibition of inflammation, and immunosuppression. Here we found that GC-treated human lung carcinoma A549 cells exhibited the enhanced formation of the thick stress fibers and focal adhesions, resulting in suppression of cell migration. In a screen for GC-responsive genes encoding actin-interacting proteins, we identified caldesmon (CaD), which is specifically up-regulated in response to GCs. CaD is a regulatory protein involved in actomyosin-based contraction and the stability of actin filaments. We further demonstrated that the up-regulation of CaD expression was controlled by glucocorticoid receptor (GR). An activated form of GR directly bound to the two glucocorticoidresponse element-like sequences in the human CALD1 promoter and transactivated the CALD1 gene, thereby up-regulating the CaD protein. Forced expression of CaD, without GC treatment, also enhanced the formation of thick stress fibers and focal adhesions and suppressed cell migration. Conversely, depletion of CaD abrogated the GC-induced phenotypes. The results of this study suggest that the GR-dependent up-regulation of CaD plays a pivotal role in regulating cell migration via the reorganization of the actin cytoskeleton.

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Section: Glucocorticoids Suppress Cell Migration and Reorganize The Amentioning

confidence: 86%

Section: Discussionmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

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Glucocorticoid Receptor-mediated Expression of Caldesmon Regulates Cell Migration via the Reorganization of the Actin Cytoskeleton

Mayanagi¹,

Morita

Hayashi

et al. 2008

Journal of Biological Chemistry

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“…Myocardinlike proteins 1 and 2 (MKL1 and MKL2, respectively), which are co-activators of SRF, also have a key role in controlling Rhodependent gene expression and cell growth (Descot et al, 2008). RhoA regulates the nuclear translocation of MKL1 and/or MKL2 and mediates the formation of stress fibers and focal adhesions by activating the transcription of cytoskeletal and/or focal adhesion genes (Morita et al, 2007).…”

Section: The Cytoskeleton As a Regulator Of Transcriptionmentioning

confidence: 99%

Mechanosensitive mechanisms in transcriptional regulation

Mammoto

Ingber

2012

Journal of Cell Science

344

291

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SummaryTranscriptional regulation contributes to the maintenance of pluripotency, self-renewal and differentiation in embryonic cells and in stem cells. Therefore, control of gene expression at the level of transcription is crucial for embryonic development, as well as for organogenesis, functional adaptation, and regeneration in adult tissues and organs. In the past, most work has focused on how transcriptional regulation results from the complex interplay between chemical cues, adhesion signals, transcription factors and their co-regulators during development. However, chemical signaling alone is not sufficient to explain how three-dimensional (3D) tissues and organs are constructed and maintained through the spatiotemporal control of transcriptional activities. Accumulated evidence indicates that mechanical cues, which include physical forces (e.g. tension, compression or shear stress), alterations in extracellular matrix (ECM) mechanics and changes in cell shape, are transmitted to the nucleus directly or indirectly to orchestrate transcriptional activities that are crucial for embryogenesis and organogenesis. In this Commentary, we review how the mechanical control of gene transcription contributes to the maintenance of pluripotency, determination of cell fate, pattern formation and organogenesis, as well as how it is involved in the control of cell and tissue function throughout embryogenesis and adult life. A deeper understanding of these mechanosensitive transcriptional control mechanisms should lead to new approaches to tissue engineering and regenerative medicine. IntroductionTissue and organ architecture are constructed as a result of the complex orchestration of various cell types that exhibit specific behaviors (e.g. growth, differentiation, migration and apoptosis) in specific locations at precise times during embryogenesis. Transcriptional programs confer and maintain cellular identity and functions that are necessary for the maturation of embryonic cells into terminally differentiated tissues or organs, as well as for stem cell fate switching throughout adult life. These behaviors are regulated by turning genes on and off in a highly spatiotemporally controlled manner, and this process is mediated at the level of gene transcription through the interplay between RNA polymerase II, various transcription factors and their co-regulators (Box 1). Whereas most studies on transcriptional regulation have focused on genetic or chemical control mechanisms of transcription, recent work suggests that mechanical forces (Box 2) are equally important regulators of transcriptional control in embryonic and adult tissues. In this Commentary, we review these new insights into cellular mechanotransduction, and discuss how mechanical cues influence transcriptional regulation to govern organogenesis and to ensure tissue maintenance throughout adult life.

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“…These included the MAPK, cyclic adenosine monophosphate-dependent protein kinase A (RAS/cAMP-PKA), target of rapamycin (TOR) and the ceramide stress response pathways (Schubert et al, 2006;Harispe et al, 2008;Dunlop and Tee, 2009;Levin, 2005;Morita et al, 2007). Key putative regulators and effectors of these pathways (Faix and Grosses, 2006;Harispe et al, 2008;Bastidas et al, 2009) were identified in this study.…”

Section: Discussionmentioning

confidence: 93%

Gene expression associated with vegetative incompatibility in Amylostereum areolatum

Nest¹,

Steenkamp²,

Slippers³

et al. 2011

Fungal Genetics and Biology

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In filamentous fungi, vegetative compatibility among individuals of the same species is determined by the genes encoded at the heterokaryon incompatibility (het) loci. The hyphae of genetically similar individuals that share the same allelic specificities at their het loci are able to fuse and intermingle, while different allelic specificities at the het loci result in cell death of the interacting hyphae. In this study, suppression subtractive hybridization (SSH) followed by pyrosequencing and quantitative reverse transcription PCR were used to identify genes that are selectively expressed when vegetatively incompatible individuals of Amylostereum areolatum interact. The SSH library contained genes associated with various cellular processes, including cell-cell adhesion, stress and defence responses, as well as cell death. Some of the transcripts encoded proteins that were previously implicated in the stress and defence responses associated with vegetative incompatibility. Other transcripts encoded proteins known to be associated with programmed cell death, but have not previously been linked with vegetative incompatibility.Results of this study have considerably increased our knowledge of the processes underlying vegetative incompatibility in Basidiomycetes in general and A. areolatum in particular.

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Reorganization of the actin cytoskeleton via transcriptional regulation of cytoskeletal/focal adhesion genes by myocardin-related transcription factors (MRTFs/MAL/MKLs)

Cited by 64 publications

References 33 publications

Glucocorticoid Receptor-mediated Expression of Caldesmon Regulates Cell Migration via the Reorganization of the Actin Cytoskeleton

Glucocorticoid Receptor-mediated Expression of Caldesmon Regulates Cell Migration via the Reorganization of the Actin Cytoskeleton

Mechanosensitive mechanisms in transcriptional regulation

Gene expression associated with vegetative incompatibility in Amylostereum areolatum

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