Conditional Ablation of Nonmuscle Myosin II-B Delineates Heart Defects in Adult Mice

Ma, Xuefei; Takeda, Kazuyo; Singh, Aman; Yu, Zu‐Xi; Zerfas, Patricia M.; Blount, Anthony; Liu, Chengyu; Towbin, Jeffrey A.; Schneider, Michael; Adelstein, Robert S.; Wei, Qize

doi:10.1161/circresaha.109.200303

Cited by 69 publications

(79 citation statements)

References 25 publications

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“…This might be because of the high level of expression of MIIA compared with other isoforms (83%67, MIIA; 17%67, MIIB) (Ma et al, 2009). It has been shown previously that MII is required for migration in restricted environments wherein Dictyostelium migration is slowed in under-agarose cell migration assays (Laevsky and Knecht, 2003).…”

Section: Discussionmentioning

confidence: 99%

Microenvironmental control of cell migration: Myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics

Doyle

Kutys

Conti

et al. 2012

Journal of Cell Science

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111

112

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SummaryRecent evidence suggests that organization of the extracellular matrix (ECM) into aligned fibrils or fibril-like ECM topographies promotes rapid migration in fibroblasts. However, the mechanisms of cell migration that are altered by these changes in microenvironmental topography remain unknown. Here, using 1D fibrillar migration as a model system for oriented fibrillar 3D matrices, we find that fibroblast leading-edge dynamics are enhanced by 1D fibrillar micropatterns and demonstrate a dependence on the spatial positioning of cell adhesions. Although 1D, 2D and 3D matrix adhesions have similar assembly kinetics, both 1D and 3D adhesions are stabilized for prolonged periods, whereas both paxillin and vinculin show slower turnover rates in 1D adhesions. Moreover, actin in 1D adhesions undergoes slower retrograde flow than the actin that is present in 2D lamellipodia. These data suggest an increase in mechanical coupling between adhesions and protrusive machinery. Experimental reduction of contractility resulted in the loss of 1D adhesion structure and stability, with scattered small and unstable adhesions, and an uncoupling of adhesion protein-integrin stability. Genetic ablation of myosin IIA (MIIA) or myosin IIB (MIIB) isoforms revealed that MIIA is required for efficient migration in restricted environments as well as adhesion maturation, whereas MIIB helps to stabilize adhesions beneath the cell body. These data suggest that restricted cell environments, such as 1D patterns, require cellular contraction through MIIA to enhance adhesion stability and coupling to integrins behind the leading edge. This increase in mechanical coupling allows for greater leading-edge protrusion and rapid cell migration.

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Section: Discussionmentioning

confidence: 99%

Microenvironmental control of cell migration: Myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics

Doyle

Kutys

Conti

et al. 2012

Journal of Cell Science

Self Cite

111

112

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“…B − /B − , B flox /B flox , and B GFP /B GFP mice were generated as previously described (Bao et al, 2007;Ma et al, 2009;Tullio et al, 1997) and are available through the Mutant Mouse Regional Resource Centers (MMRRC, #16991and #37053). WT-1 Cre mice were generously provided by Dr William Pu (Boston Children's Hospital, Boston, MA).…”

Section: Animalsmentioning

confidence: 99%

Nonmuscle myosin IIB regulates epicardial integrity and epicardium-derived mesenchymal cell maturation

Sung

Yang

et al. 2017

Journal of Cell Science

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Nonmuscle myosin IIB (NMIIB; heavy chain encoded by MYH10) is essential for cardiac myocyte cytokinesis. The role of NMIIB in other cardiac cells is not known. Here, we show that NMIIB is required in epicardial formation and functions to support myocardial proliferation and coronary vessel development. Ablation of NMIIB in epicardial cells results in disruption of epicardial integrity with a loss of E-cadherin at cell-cell junctions and a focal detachment of epicardial cells from the myocardium. NMIIB-knockout and blebbistatin-treated epicardial explants demonstrate impaired mesenchymal cell maturation during epicardial epithelial-mesenchymal transition. This is manifested by an impaired invasion of collagen gels by the epicardium-derived mesenchymal cells and the reorganization of the cytoskeletal structure. Although there is a marked decrease in the expression of mesenchymal genes, there is no change in Snail (also known as Snai1) or E-cadherin expression. Studies from epicardiumspecific NMIIB-knockout mice confirm the importance of NMIIB for epicardial integrity and epicardial functions in promoting cardiac myocyte proliferation and coronary vessel formation during heart development. Our findings provide a novel mechanism linking epicardial formation and epicardial function to the activity of the cytoplasmic motor protein NMIIB.

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“…36 smMLCK may phosphorylate non-muscle cytoplasmic myosin II-B and plays an important role in the heart. 37 Thus, there are currently 2 candidate kinases for MLC2 phosphorylation in cardiac myocytes: cMLCK 7,18 and zipper-interacting PK (ZIPK). 38 ZIPK is a Ca 2+ -independent serine/threonine kinase that has been implicated in apoptosis and is ubiquitously expressed, including in adult and neonatal cardiac myocytes.…”

Section: Pks and Protein Phosphatase Regulation Of Mlc2 Phosphorylatimentioning

confidence: 99%

Biochemical and Physiological Regulation of Cardiac Myocyte Contraction by Cardiac-Specific Myosin Light Chain Kinase

Tsukamoto

Kitakaze

2013

Circ J

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Conditional Ablation of Nonmuscle Myosin II-B Delineates Heart Defects in Adult Mice

Cited by 69 publications

References 25 publications

Microenvironmental control of cell migration: Myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics

Microenvironmental control of cell migration: Myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics

Nonmuscle myosin IIB regulates epicardial integrity and epicardium-derived mesenchymal cell maturation

Biochemical and Physiological Regulation of Cardiac Myocyte Contraction by Cardiac-Specific Myosin Light Chain Kinase

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