NMII Forms a Contractile Transcellular Sarcomeric Network to Regulate Apical Cell Junctions and Tissue Geometry

Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Current biology: CB (Impact Factor: 9.57). 04/2013; 23(8). DOI: 10.1016/j.cub.2013.03.039
Source: PubMed


Nonmuscle myosin II (NMII) is thought to be the master integrator of force within epithelial apical junctions, mediating epithelial tissue morphogenesis and tensional homeostasis [1-3]. Mutations in NMII are associated with a number of diseases due to failures in cell-cell adhesion [4-8]. However, the organization and the precise mechanism by which NMII generates and responds to tension along the intercellular junctional line are still not known. We discovered that periodic assemblies of bipolar NMII filaments interlace with perijunctional actin and α-actinin to form a continuous belt of muscle-like sarcomeric units (∼400-600 nm) around each epithelial cell. Remarkably, the sarcomeres of adjacent cells are precisely paired across the junctional line, forming an integrated, transcellular contractile network. The contraction/relaxation of paired sarcomeres concomitantly impacts changes in apical cell shape and tissue geometry. We show differential distribution of NMII isoforms across heterotypic junctions and evidence for compensation between isoforms. Our results provide a model for how NMII force generation is effected along the junctional perimeter of each cell and communicated across neighboring cells in the epithelial organization. The sarcomeric network also provides a well-defined target to investigate the multiple roles of NMII in junctional homeostasis as well as in development and disease.

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Available from: Seham Ebrahim, Jan 29, 2015
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    • "Earlier confocal analyses showed that both NMIIA and NMIIB concentrate at the ZA in confluent MCF-7 monolayers and contribute to its morphological integrity (McLachlan and Yap, 2011; Smutny et al., 2011). Now, by applying higher resolution imaging with Structured Illumination Microscopy (SIM) we further find that both paralogs localize in puncta overlying the apical actin rings (Figure 1A), which may correspond to the sarcomeric-like organization of actomyosin seen at epithelial junctions in tissues (Ebrahim et al., 2013). "
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    ABSTRACT: Cell-cell adhesion couples the contractile cortices of epithelial cells together, generating tension to support a range of morphogenetic processes. E-cadherin adhesion plays an active role in generating junctional tension, by promoting actin assembly and cortical signaling pathways that regulate Myosin II. Multiple Myosin II paralogs accumulate at mammalian epithelial cell-cell junctions. Earlier we found that Myosin IIA responds to Rho-ROCK signaling to support junctional tension in MCF-7 cells. Although Myosin IIB is also found at the zonula adherens (ZA) in these cells, its role in junctional contractility, and its mode of regulation, are less well understood. We now demonstrate that Myosin IIB contributes to tension at the epithelial ZA. Further, we identify a RPTPα-SFK-Rap1 pathway as responsible for recruiting Myosin IIB to the ZA and supporting contractile tension. Overall, these findings reinforce the concept that orthogonal E-cadherin-based signaling pathways recruit distinct Myosin II paralogs to generate the contractile apparatus at apical epithelial junctions. © 2015 by The American Society for Cell Biology.
    Molecular Biology of the Cell 01/2015; 26(7). DOI:10.1091/mbc.E14-07-1223 · 4.47 Impact Factor
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    • "This regulation controls the amount of AJ proteins incorporated into AJs, their lateral mobility, and their removal from AJs. From the plasticity of migrating clusters of cells [11] to the stable epithelium of the organ of Corti [12], the protein interaction networks formed by AJs can have a range of dynamic properties. However, we are just beginning to acquire an integrated view of these dynamics and how they are regulated. "
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    ABSTRACT: During Drosophila gastrulation, amnioserosa (AS) cells flatten and spread as an epithelial sheet. We used AS morphogenesis as a model to investigate how adherens junctions (AJs) distribute along elongating cell-cell contacts in vivo. As the contacts elongated, total AJ protein levels increased along their length. However, genetically blocking this AJ addition indicated that it was not essential for maintaining AJ continuity. Implicating other remodeling mechanisms, AJ photobleaching revealed non-directional lateral mobility of AJs along the elongating contacts, as well as local AJ removal from the membranes. Actin stabilization with jasplakinolide reduced AJ redistribution, and live imaging of myosin II along elongating contacts revealed fragmented, expanding and contracting actomyosin networks, suggesting a mechanism for lateral AJ mobility. Actin stabilization also increased total AJ levels, suggesting an inhibition of AJ removal. Implicating AJ removal by endocytosis, clathrin endocytic machinery accumulated at AJs. However, dynamin disruption had no apparent effect on AJs, suggesting the involvement of redundant or dynamin-independent mechanisms. Overall, we propose that new synthesis, lateral diffusion, and endocytosis play overlapping roles to populate elongating cell-cell contacts with evenly distributed AJs in this in vivo system.
    PLoS ONE 11/2013; 8(11):e79613. DOI:10.1371/journal.pone.0079613 · 3.23 Impact Factor
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    ABSTRACT: Claudins form the paracellular tight junction seal in epithelial tissues. Although there is still limited information on how these proteins are organized at the junction, a number of recent studies have provided useful insights both into claudin-claudin interactions and into interactions between claudins and other proteins. The focus of this review is to summarize recent information about claudin interactions and to identify critical unanswered questions about claudin organization and tight junction structure which will be required to understand claudin function.
    07/2013; 1(3):e25247. DOI:10.4161/tisb.25247
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