Nonmuscle Myosin II Regulation Directs Its Multiple Roles in Cell Migration and Division

Abstract

Nonmuscle myosin II (NMII) is a multimeric protein complex that generates most mechanical force in eukaryotic cells. NMII function is controlled at three main levels. The first level includes events that trigger conformational changes that extend the complex to enable its assembly into filaments. The second level controls the ATPase activity of the complex and its binding to microfilaments in extended NMII filaments. The third level includes events that modulate the stability and contractility of the filaments. They all work in concert to finely control force generation inside cells. NMII is a common endpoint of mechanochemical signaling pathways that control cellular responses to physical and chemical extracellular cues. Specific phosphorylations modulate NMII activation in a context-dependent manner. A few kinases control these phosphorylations in a spatially, temporally, and lineage-restricted fashion, enabling functional adaptability to the cellular microenvironment. Here, we review mechanisms that control NMII activity in the context of cell migration and division. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

A myosin chaperone, UNC‐45A, is a novel regulator of intestinal epithelial barrier integrity and repair

“…NM-II is a crucial cytoskeletal motor that regulates assembly and functions of epithelial apical junctions and basal ECM adhesions. 12 , 57 , 58 Although molecular mechanisms that govern NM-II ATPase activity and its dynamic interactions with actin filaments have been extensively investigated, much less is known about the regulation of NM-II organization into higher-order contractile structures associated with epithelial adhesive complexes. In this study we describe a novel mechanism controlling NM-II-dependent assembly of apical junctions and ECM adhesions that is essential for the integrity and repair of the intestinal epithelial barrier.…”

Cytoskeletal Remodelling as an Achilles’ Heel for Therapy Resistance in Melanoma

“…The actomyosin filament network, along with other components, makes up the cytoskeleton that gives shape to the cells [79]. The actomyosin cytoskeleton additionally generates the contractile force that enables cytokinesis, cell motility, migration, invasion, and force-mediated extracellular matrix (ECM) remodelling, among other fundamental processes [79][80][81].…”

“…The cytoskeleton and its regulators are not commonly mutated in melanoma (except RAC1 P29S ) [12]. Therefore, targeting the cytoskeleton, which is essential for many physiological processes in non-tumour cells (cytokinesis, muscle contraction, and the migration of immune cells, among others) [79,81], could provoke undesirable toxicity. However, as with oncogenes (specifically, BRAF V600E ), tumour cells (in particular, therapy-resistant cells) appear to be somehow "addicted" to the cytoskeletal's remodelling signals, which would presumably lower the threshold for the effective targeting without affecting excessively normal cells.…”

Endothelial Cell Plasma Membrane Biomechanics Mediates Effects of Pro-Inflammatory Factors on Endothelial Mechanosensors: Vicious Circle Formation in Atherogenic Inflammation

“…NMMII is an actin-based heterohexameric molecular motor consisting of two heavy chains (HCs), two essential light chains (ELCs), and two regulatory light chains (RLCs) [74][75][76][77][78]. There are three isoforms of NMMII depending on HC paralog: NMMIIA, NMMIIB, and NMMIIC [74][75][76][77], which apparently have partially distinctive roles [79].…”