Mechanoregulation of h2-Calponin Gene Expression and the Role of Notch Signaling

Jiang, Wenrui; Cady, Geoffrey; Hossain, Mokarram; Huang, Qinglan; Wang, Xin; Jin, Jian‐Ping

doi:10.1074/jbc.m113.498147

Cited by 25 publications

(38 citation statements)

References 51 publications

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“…In addition to CNN3, CNN2 is also expressed in nonmuscle cells (Wu and Jin, 2008). Interestingly, expression of CNN2 is reportedly upregulated under conditions in which cytoskeletal tension is higher (Hossain et al, 2005(Hossain et al, , 2006Jiang et al, 2014). Given that CNN2 stabilizes actin stress fibers (Hossain et al, 2005), the cytoskeletal-tension-dependent increase in CNN2 expression might also participate in a positive feedback type of cellular contractility regulation.…”

Section: Discussionmentioning

confidence: 99%

MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility

Harai

Yip

et al. 2016

Journal of Cell Science

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MEKK1 (also known as MAP3K1), which plays a major role in MAPK signaling, has been implicated in mechanical processes in cells, such as migration. Here, we identify the actin-binding protein calponin-3 as a new MEKK1 substrate in the signaling that regulates actomyosinbased cellular contractility. MEKK1 colocalizes with calponin-3 at the actin cytoskeleton and phosphorylates it, leading to an increase in the cell-generated traction stress. MEKK1-mediated calponin-3 phosphorylation is attenuated by the inhibition of myosin II activity, the disruption of actin cytoskeletal integrity and adhesion to soft extracellular substrates, whereas it is enhanced upon cell stretching. Our results reveal the importance of the MEKK1-calponin-3 signaling pathway to cell contractility.

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Section: Discussionmentioning

confidence: 99%

MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility

Harai

Yip

et al. 2016

Journal of Cell Science

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“…Calponin 2 is found in a broader range of tissue and cell types, including developing and remodeling smooth muscles and adult mature smooth muscles (Hossain et al, 2003), epidermal keratinocytes (Fukui et al, 1997), fibroblasts (Hossain et al, 2005), lung alveolar cells (Hossain et al, 2006), endothelial cells (Tang et al, 2006), myeloid white blood cells (Huang et al, 2008), myoblasts (Jiang et al, 2014), prostate cancer cells (Hossain et al, 2014) and platelets (Hines et al, 2014). These cell types can be paced in three groups: a) cells that are physiologically under high mechanical tension, e.g., smooth muscle cells in the wall of hollow organs, epithelial and endothelial cells; b) cells that have high rates of proliferation, e.g., myoblasts; and c) cells that are actively migrating, e.g., fibroblasts and macrophages.…”

Section: Tissue and Cell Type-specific Expression Of Calponin Isofmentioning

confidence: 99%

“…Calponin 2 is expressed in smooth muscle and multiple types of non-muscle cells, such as epidermal keratinocytes (Hossain et al, 2005), lung alveolar cells (Hossain et al, 2006), endothelial cells (Tang et al, 2006), fibroblasts (Hossain et al, 2005), blood cells of myeloid lineages (Huang et al, 2008), lymphocytes (Flemming et al, 2015), epithelial cells, myoblasts (Jiang et al, 2014), prostate gland epithelial cells (Hossain et al, 2014) and platelets (Hines et al, 2014). Like calponin 1 in smooth muscle cells, calponin 2 is an actin-binding protein associated with the actin cytoskeleton of smooth muscle and a broad range of non-muscle cells.…”

Section: Biological Functions Of Calponinmentioning

confidence: 99%

“…Deletion and site-specific mutagenesis experiments identified the role of a binding site for transcriptional factor HES-1 (hairy and enhancer of split 1) in the 5′-upstream region of mouse Cnn2 promoter (Jiang et al, 2014). Deletion or mutation of the HES-1 site in mouse Cnn2 promoter abolished the mechanical regulation and resulted in a substrate stiffness independent high level of transcriptional activity.…”

Section: Regulation Of Calponin Functionsmentioning

confidence: 99%

“…Therefore, the regulatory mechanism is via a low tension-induced repression of transcription. Corresponding to the down-regulation of Cnn2 gene expression, the level of HES-1 increased in cells cultured on soft gel substrates in comparison with that in cells cultured on hard gels (Jiang et al, 2014). HES-1 is known to function downstream of the Notch-RBP J signaling pathway (Kageyama et al, 1997), which has been suggested to mediate cellular mechanoregulations (Morrow et al, 2005; Morrow et al, 2007).…”

Section: Regulation Of Calponin Functionsmentioning

confidence: 99%

See 2 more Smart Citations

Calponin isoforms CNN 1, CNN 2 and CNN 3: Regulators for actin cytoskeleton functions in smooth muscle and non-muscle cells

Liu

Jin

2016

Gene

Self Cite

144

140

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Calponin is an actin filament-associated regulatory protein expressed in smooth muscle and multiple types of non-muscle cells. Three homologous genes, CNN1, CNN2 and CNN3, encoding calponin isoforms 1, 2, and 3, respectively, are present in vertebrate species. All three calponin isoforms are actin-binding proteins with functions in inhibiting actin-activated myosin ATPase and stabilizing the actin cytoskeleton, while each isoform executes different physiological roles based on their cell type-specific expressions. Calponin 1 is specifically expressed in smooth muscle cells and plays a role in fine-tuning smooth muscle contractility. Calponin 2 is expressed in both smooth muscle and non-muscle cells and regulates multiple actin cytoskeleton-based functions. Calponin 3 participates in actin cytoskeleton-based activities in embryonic development and myogenesis. Phosphorylation has been extensively studied for the regulation of calponin functions. Cytoskeleton tension regulates the transcription of CNN2 gene and the degradation of calponin 2 protein. This review summarizes our knowledge learned from studies over the past three decades, focusing on the evolutionary lineage of calponin isoform genes, their tissue- and cell type-specific expressions, structure-function relationships, and mechanoregulation.

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Tethered Jagged-1 Synergizes with Culture Substrate Stiffness to Modulate Notch-Induced Myogenic Progenitor Differentiation

et al. 2017

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Introduction-Notch signaling is amongst the key intrinsic mechanisms regulating satellite cell fate, promoting the transition of activated satellite cells to highly proliferative myogenic progenitor cells and preventing their premature differentiation. Although much is known about the biochemical milieu that drives myogenic progression, less is known about the spatial cues providing spatiotemporal control of skeletal muscle repair in the context of Notch signaling. Methods-Using a murine injury model, we quantified in vivo biophysical changes that occur within the skeletal muscle during regeneration. Employing tunable poly(ethylene glycol)-based hydrogel substrates, we modeled the measured changes in bulk stiffness in the context of Notch ligand signaling, which are present in the regenerative milieu at the time of injury. Results-Following injury, there is a transient increase in the bulk stiffness of the tibialis anterior muscle that may be explained in part by changes in extracellular matrix deposi-tion. When presented to primary myoblasts, Jagged-1, Jagged-2, and Dll1 in a tethered format elicited greater degrees of Notch activity compared to their soluble form. Only tethered Jagged-1 effects were tuned by substrate stiffness, with the greatest Notch activation observed on stiff hydrogels matching the stiffness of regenerating muscle. When exposed to tethered Jagged-1 on stiff hydrogels, fewer primary myoblasts expressed myogenin, and pharmacological inhibitor studies suggest this effect is Notch and RhoA dependent. Conclusion-Our study proposes that tethered Jagged-1 presented in the context of transient tissue stiffening serves to tune Notch activity in myogenic progenitors during skeletal muscle repair and delay differentiation.

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Mechanoregulation of h2-Calponin Gene Expression and the Role of Notch Signaling

Cited by 25 publications

References 51 publications

MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility

MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility

Calponin isoforms CNN 1, CNN 2 and CNN 3: Regulators for actin cytoskeleton functions in smooth muscle and non-muscle cells

Tethered Jagged-1 Synergizes with Culture Substrate Stiffness to Modulate Notch-Induced Myogenic Progenitor Differentiation

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