Myosin Light Chain Kinase (MLCK) Regulates Cell Migration in a Myosin Regulatory Light Chain Phosphorylation-independent Mechanism

Chen, Chen; Tao, Tao; Wen, Cheng P.; He, Wei–Qi; Qiao, Yan; Gao, Yun‐Qian; Chen, Xin; Wang, Pei; Chen, Caiping; Zhao, Wei; Chen, Huaqun; Ye, An-Pei; Peng, Yi; Zhu, Min–Sheng

doi:10.1074/jbc.m114.567446

Cited by 65 publications

(48 citation statements)

References 76 publications

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“…FA assembly, growth and maintenance depend on actomyosin traction forces, which adapt to the substrate elasticity (Burridge and Wittchen, 2013). In spite of alternative pathways involving MRCK (which has two isoforms, MRCKα and MRCKβ, also known as CDC42BPA and CDC42BPB, respectively), MLCK (also known as MYLK) or mDia (Burridge and Wittchen, 2013;Chen et al, 2014;Jégou et al, 2013;Totsukawa et al, 2004), a key event is the modulation of cellular contractility through myosin-based contractility and ROCK (which has two isoforms, ROCK1 and ROCK2) activity. However, signaling pathways underlying FA-mediated rigidity sensing and the mechano-response are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

ICAP-1 monoubiquitylation coordinates matrix density and rigidity sensing for cell migration through ROCK2–MRCKα balance

Bouin

Kyumurkov

Régent-Kloeckner

et al. 2017

Journal of Cell Science

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There was an error published in J. Cell Sci. 130, 626-636.The name of the author Alexander Kyumurkov was incorrect in the original author list. The correct spelling is given above.The authors apologise to the readers for any confusion that this error might have caused. 1195 ABSTRACTCell migration is a complex process requiring density and rigidity sensing of the microenvironment to adapt cell migratory speed through focal adhesion and actin cytoskeleton regulation. ICAP-1 (also known as ITGB1BP1), a β1 integrin partner, is essential for ensuring integrin activation cycle and focal adhesion formation. We show that ICAP-1 is monoubiquitylated by Smurf1, preventing ICAP-1 binding to β1 integrin. The non-ubiquitylatable form of ICAP-1 modifies β1 integrin focal adhesion organization and interferes with fibronectin density sensing. ICAP-1 is also required for adapting cell migration in response to substrate stiffness in a β1-integrin-independent manner. ICAP-1 monoubiquitylation regulates rigidity sensing by increasing MRCKα (also known as CDC42BPA)-dependent cell contractility through myosin phosphorylation independently of substrate rigidity. We provide evidence that ICAP-1 monoubiquitylation helps in switching from ROCK2-mediated to MRCKα-mediated cell contractility. ICAP-1 monoubiquitylation serves as a molecular switch to coordinate extracellular matrix density and rigidity sensing thus acting as a crucial modulator of cell migration and mechanosensing.

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Section: Introductionmentioning

confidence: 99%

ICAP-1 monoubiquitylation coordinates matrix density and rigidity sensing for cell migration through ROCK2–MRCKα balance

Bouin

Kyumurkov

Régent-Kloeckner

et al. 2017

Journal of Cell Science

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“…Cell movement involves tight regulation of F-actin-binding and non-muscle myosin II activity to control membrane tension and protrusion necessary for migration (Watanabe et al, 2007;Chen et al, 2014). Actomyosin contractions are also thought to be major contributors to the tensions observed at the cell-cell interfaces (Fernandez-Gonzalez and Zallen, 2009;Mason and Martin, 2011;Brodland et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair

Franco

Atieh

Bryan

et al. 2018

Preprint

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Epithelial wound healing requires a complex orchestration of cellular rearrangements and movements to restore tissue architecture and function after injury. While it is well-known that mechanical forces can affect tissue morphogenesis and patterning, how the biophysical cues generated after injury influence cellular behaviors during tissue repair is not well understood.Using time-lapsed confocal imaging of epithelial tissues in living zebrafish larvae, we provide evidence that localized increases in cellular crowding during wound closure promote the extrusion of non-apoptotic cells via mechanically regulated stretch-activated ion channels (SACs). Directed cell migration toward the injury site promoted the rapid changes in cell number and generated shifts in tension at cellular interfaces over long spatial distances. Perturbation of SAC activity resulted in failed extrusion and increased proliferation in crowded areas of the tissue. Together, we conclude that localized cell number plays a key role in dictating cellular behaviors that facilitate wound closure and tissue repair.

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“…Third, the failure of long MLCK knockout to limit severity of DSS colitis is readily understood when one considers the critical role of MLCK in cell migration and wound healing (Russo et al 2005; Chen et al 2014). Thus, although some have expressed surprise at the failure of MLCK inhibition to prevent colitis induced by chemical injury or epithelial apoptosis and therefore questioned whether MLCK is a relevant therapeutic target, the protection of long MLCK knockout mice from immune-mediated experimental IBD, but not direct epithelial injury, is expected.…”

Section: Tumor Necrosis Factor-mediated Regulation Of Tight Junction mentioning

confidence: 99%

Cell Biology of Tight Junction Barrier Regulation and Mucosal Disease

Buckley

Turner

2017

Cold Spring Harb Perspect Biol

535

370

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Mucosal surfaces are lined by epithelial cells. In the intestine, the epithelium establishes a selectively permeable barrier that supports nutrient absorption and waste secretion while preventing intrusion by luminal materials. Intestinal epithelia therefore play a central role in regulating interactions between the mucosal immune system and luminal contents, which include dietary antigens, a diverse intestinal microbiome, and pathogens. The paracellular space is sealed by the tight junction, which is maintained by a complex network of protein interactions. Tight junction dysfunction has been linked to a variety of local and systemic diseases. Two molecularly and biophysically distinct pathways across the intestinal tight junction are selectively and differentially regulated by inflammatory stimuli. This review discusses the mechanisms underlying these events, their impact on disease, and the potential of using these as paradigms for development of tight junction-targeted therapeutic interventions.

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Myosin Light Chain Kinase (MLCK) Regulates Cell Migration in a Myosin Regulatory Light Chain Phosphorylation-independent Mechanism

Cited by 65 publications

References 76 publications

ICAP-1 monoubiquitylation coordinates matrix density and rigidity sensing for cell migration through ROCK2–MRCKα balance

ICAP-1 monoubiquitylation coordinates matrix density and rigidity sensing for cell migration through ROCK2–MRCKα balance

Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair

Cell Biology of Tight Junction Barrier Regulation and Mucosal Disease

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