Abstract:ABSTRACTThe mechanical properties of the cellular cortex regulate shape changes during cell division, cell migration and tissue morphogenesis. During cell division, contractile force generated by the molecular motor myosin II (MII) at the equatorial cortex drives cleavage furrow ingression. Cleavage furrow ingression in turn increases stresses at the polar cortex, where contractility must be regulated to maintain cell shape during cytokinesis. How polar cortex contractility con… Show more
“…However, there could also be molecular contexts in which the redundancy between paralogs is not enough and the unique properties of NMII-A are crucial. These properties are determined mostly by the dynamic properties of the head (the higher ATPase activity, lower duty ratio than the other paralogs) [ 109 ] but also by the tail, that determine cellular localization and filament stability [ 19 , 110 , 111 ].…”
Section: Three Hypotheses To Explain the Correlation Between Genotmentioning
confidence: 99%
“…A similar case is that of the formation of the cytokinesis ring. A recent study from the Burnette group has shown that NMII-A/B chimeras are directed to the cytokinesis ring through their tail domains, but the head domain swap decreases separation efficiency [ 111 ], lending support to the argument that full activation of one specific paralog may be required for some functions. In other instances, other fully competent myosin paralogs may compensate for this, if present.…”
Section: Why Do Myh9-rd Patients Display Few But Giant Plateletsmentioning
The MYH9 gene encodes the heavy chain (MHCII) of non-muscle myosin II A (NMII-A). This is an actin-binding molecular motor essential for development that participates in many crucial cellular processes such as adhesion, cell migration, cytokinesis and polarization, maintenance of cell shape and signal transduction. Several types of mutations in the MYH9 gene cause an array of autosomal dominant disorders, globally known as MYH9-related diseases (MYH9-RD). These include May-Hegglin anomaly (MHA), Epstein syndrome (EPS), Fechtner syndrome (FTS) and Sebastian platelet syndrome (SPS). Although caused by different MYH9 mutations, all patients present macrothrombocytopenia, but may later display other pathologies, including loss of hearing, renal failure and presenile cataracts. The correlation between the molecular and cellular effects of the different mutations and clinical presentation are beginning to be established. In this review, we correlate the defects that MYH9 mutations cause at a molecular and cellular level (for example, deficient filament formation, altered ATPase activity or actin-binding) with the clinical presentation of the syndromes in human patients. We address why these syndromes are tissue restricted, and the existence of possible compensatory mechanisms, including residual activity of mutant NMII-A and/or the formation of heteropolymers or co-polymers with other NMII isoforms.
“…However, there could also be molecular contexts in which the redundancy between paralogs is not enough and the unique properties of NMII-A are crucial. These properties are determined mostly by the dynamic properties of the head (the higher ATPase activity, lower duty ratio than the other paralogs) [ 109 ] but also by the tail, that determine cellular localization and filament stability [ 19 , 110 , 111 ].…”
Section: Three Hypotheses To Explain the Correlation Between Genotmentioning
confidence: 99%
“…A similar case is that of the formation of the cytokinesis ring. A recent study from the Burnette group has shown that NMII-A/B chimeras are directed to the cytokinesis ring through their tail domains, but the head domain swap decreases separation efficiency [ 111 ], lending support to the argument that full activation of one specific paralog may be required for some functions. In other instances, other fully competent myosin paralogs may compensate for this, if present.…”
Section: Why Do Myh9-rd Patients Display Few But Giant Plateletsmentioning
The MYH9 gene encodes the heavy chain (MHCII) of non-muscle myosin II A (NMII-A). This is an actin-binding molecular motor essential for development that participates in many crucial cellular processes such as adhesion, cell migration, cytokinesis and polarization, maintenance of cell shape and signal transduction. Several types of mutations in the MYH9 gene cause an array of autosomal dominant disorders, globally known as MYH9-related diseases (MYH9-RD). These include May-Hegglin anomaly (MHA), Epstein syndrome (EPS), Fechtner syndrome (FTS) and Sebastian platelet syndrome (SPS). Although caused by different MYH9 mutations, all patients present macrothrombocytopenia, but may later display other pathologies, including loss of hearing, renal failure and presenile cataracts. The correlation between the molecular and cellular effects of the different mutations and clinical presentation are beginning to be established. In this review, we correlate the defects that MYH9 mutations cause at a molecular and cellular level (for example, deficient filament formation, altered ATPase activity or actin-binding) with the clinical presentation of the syndromes in human patients. We address why these syndromes are tissue restricted, and the existence of possible compensatory mechanisms, including residual activity of mutant NMII-A and/or the formation of heteropolymers or co-polymers with other NMII isoforms.
“…In general, epithelial monolayers undergo a variety of characteristic changes in morphology that involve dynamic physical feedback between cells. Previous studies indicated that cortical tension is related to myosin IIA activity ( 60 ). Those motility processes need to be controlled by mechanosensitive signals in order for the proper shape to be reached.…”
E-cadherin is a major cell-cell adhesion molecule involved in mechanotransduction at cell-cell contacts in tissues. Because epithelial cells respond to rigidity and tension in tissue through E-cadherin, there must be active processes that test and respond to the mechanical properties of these adhesive contacts. Using submicrometer, E-cadherin–coated polydimethylsiloxane pillars, we find that cells generate local contractions between E-cadherin adhesions and pull to a constant distance for a constant duration, irrespective of pillar rigidity. These cadherin contractions require nonmuscle myosin IIB, tropomyosin 2.1, α-catenin, and binding of vinculin to α-catenin. Cells spread to different areas on soft and rigid surfaces with contractions, but spread equally on soft and rigid without. We further observe that cadherin contractions enable cells to test myosin IIA–mediated tension of neighboring cells and sort out myosin IIA–depleted cells. Thus, we suggest that epithelial cells test and respond to the mechanical characteristics of neighboring cells through cadherin contractions.
“…The static tension chain, for which v S = 0, gives the active Young-Laplace law, with the following consequences: (1) the tension chain is straight (H = 0) if the active pressure jump p a counter-balances the (passive) elastic pressure jump p e (i.e., p e + p a = 0); (2) in the absence of a passive pressure jump (i.e., p e = 0), active pressure jump gives rise to a curved tension chain (H = − p a /γ); and (3) tension γ along the chain is constant.…”
Section: Mechanics Of Tension Chainsmentioning
confidence: 99%
“…The distribution of forces across the scale of the cell is dynamically templated by the active cytoskeleton, in particular the cell spanning assemblies of a variety of myosins together with actin filaments and their crosslinkers [1]. Cytoskeletal organisation and remodelling give the cell its dynamical shape and form [2], as well as its adaptive mechanical response [3,4]. In addition, it sets up a global scaffold for the patterning of mesoscale condensates [5] and the relative positioning of subcellular organelles [6], such as the centrosome position [7] and nuclear localization [8,9].…”
Viewed under a fluorescence microscope, the actomyosin cytoskeleton presents vivid streaks of lines together with persistent oscillatory waves. Using an active hydrodynamic approach, we show how a uniform distribution of single or mixture of contractile stresslets spontaneously segregate, followed by the formation of singular structures of high contractility (tension chains) in finite time. Simultaneously, the collection of stresslets exhibit travelling waves and swapping as a consequence of nonreciprocity. In the finite geometry of the cell, the collection of active tension chains can form an active web held together by specific anchoring at the cell boundary. On the other hand, preferential wetting at the cell boundary can reinforce active segregation in a mixture of stresslets leading to stratification.
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