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Review
. 2013 Jan;70(1):1-21.
doi: 10.1007/s00018-012-1002-9. Epub 2012 May 8.

Nonmuscle myosin-2: mix and match

Sarah M Heissler  1 , Dietmar J Manstein
Affiliations
Review

Nonmuscle myosin-2: mix and match

Sarah M Heissler et al. Cell Mol Life Sci. 2013 Jan.

Abstract

Members of the nonmuscle myosin-2 (NM-2) family of actin-based molecular motors catalyze the conversion of chemical energy into directed movement and force thereby acting as central regulatory components of the eukaryotic cytoskeleton. By cyclically interacting with adenosine triphosphate and F-actin, NM-2 isoforms promote cytoskeletal force generation in established cellular processes like cell migration, shape changes, adhesion dynamics, endo- and exo-cytosis, and cytokinesis. Novel functions of the NM-2 family members in autophagy and viral infection are emerging, making NM-2 isoforms regulators of nearly all cellular processes that require the spatiotemporal organization of cytoskeletal scaffolding. Here, we assess current views about the role of NM-2 isoforms in these activities including the tight regulation of NM-2 assembly and activation through phosphorylation and how NM-2-mediated changes in cytoskeletal dynamics and mechanics affect cell physiological functions in health and disease.

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Figures

Fig. 1
Fig. 1
Phylogenetic tree of the myosin-2 subfamily in humans according to Golomb et al. [5]. The numbers adjacent to the nodes define the overall identity of the myosin heavy chains at amino acid level. The myosin-2 family is grouped into skeletal and cardiac myosins as well as smooth and nonmuscle myosins. NM-2C constitutes a distinct branch in latter group and shows an evolutionary closer relationship to smooth muscle myosin than its isoforms NM-2A and NM-2B
Fig. 2
Fig. 2
Domain structure and composition of the NM-2 holoenzyme. The NMHC (230 kDa) consists of a N-terminal motor domain, a neck domain, and coiled–coiled domain that terminates in a nonhelical tailpiece (NHT). Two NMHC form a homodimer mediated by the formation of the coiled-coil domain within the tail fragments. The enzymatically active motor domain harbors the ATP binding site and the F-actin binding region. The neck domain of each NMHC binds two sets of light chains, the essential (ELC, 17 kDa) and the regulatory (RLC, 20 kDa) light chain. Tryptic cleavage fragments the NM-2 holoenzyme into the single-headed subfragment-1 (S1), double-headed heavy meromyosin (HMM) and light meromyosin (LMM)
Fig. 3
Fig. 3
Regulation of mammalian NM-2 enzymatic activity and assembly state. RLC kinases promote the conformational change of the inhibited (10S) to the extended NM-2 conformation (6S). The inhibited conformation is assembly-incompetent, the extended conformer assembly-competent. MLCP activity shifts the equilibrium towards the inhibited conformation. The transition to the extended conformation triggers the activation of NM-2 ATPase activity and promotes the assembly of NM-2 homodimers into bipolar filaments. NMHC phosphorylation or binding of the calcium-binding protein Mts1 promotes NM-2 filament disassembly. NMHC phosphorylation impairs Mts1 binding. Mechanisms underlying NMHC dephosphorylation are unknown
Fig. 4
Fig. 4
Schematic illustration of NM-2 cellular functions in cell migration, secretion and receptor positioning. During directed cell migration, actin polymerization and reorganization establish a protrusive leading edge at the anterior part of the cell. Cell protrusions are maintained by the contractile actomyosin network and stabilized by the formation of adhesive complexes (nascent focal adhesions) with the substratum. NM-2B localizes mainly to the lamellum, where it drives the retrograde flow. Actomyosin-mediated contractility posterior to the leading edge drive cell body retraction and translocation. Both processes coincide with the formation, growth, and maintenance of mature adhesion complexes (mature focal adhesions), which are NM-2-dependent. At the retracting rear, NM-2 is predominantly organized into stress fibers that promote local contractility. Adhesion complex disassembly causes detachment of the trailing edge from the substratum and enables cell displacement. NM-2 further mediates the cross-talk between the F-actin and the microtubule network. Actomyosin interactions further drive various processes such as vesicle transport, receptor-stimulated exocytosis of secretory vesicles, and receptor positioning
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References

    1. Conti MA, Even-Ram S, Liu C, Yamada KM, Adelstein RS. Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice. J Biol Chem. 2004;279:41263–41266. doi: 10.1074/jbc.C400352200. - DOI - PubMed
    1. Tullio AN, Accili D, Ferrans VJ, Yu ZX, Takeda K, Grinberg A, Westphal H, Preston YA, Adelstein RS. Nonmuscle myosin II-B is required for normal development of the mouse heart. Proc Natl Acad Sci USA. 1997;94:12407–12412. doi: 10.1073/pnas.94.23.12407. - DOI - PMC - PubMed
    1. Kohler S, Schaller V, Bausch AR. Collective dynamics of active cytoskeletal networks. PLoS ONE. 2011;6:e23798. doi: 10.1371/journal.pone.0023798. - DOI - PMC - PubMed
    1. Berg JS, Powell BC, Cheney RE. A millennial myosin census. Mol Biol Cell. 2001;12:780–794. - PMC - PubMed
    1. Golomb E, Ma X, Jana SS, Preston YA, Kawamoto S, Shoham NG, Goldin E, Conti MA, Sellers JR, Adelstein RS. Identification and characterization of nonmuscle myosin II-C, a new member of the myosin II family. J Biol Chem. 2004;279:2800–2808. doi: 10.1074/jbc.M309981200. - DOI - PubMed

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