Genomes and Genes
nonmuscle myosin type iia
Summary: A nonmuscle isoform of myosin type II found predominantly in platelets, lymphocytes, neutrophils and brush border enterocytes.
- Bhuwania R, Cornfine S, Fang Z, Kruger M, Luna E, Linder S. Supervillin couples myosin-dependent contractility to podosomes and enables their turnover. J Cell Sci. 2012;125:2300-14 pubmed publisher..In sum, we show here that podosome subpopulations differ in their molecular composition and identify supervillin, in cooperation with myosin IIA, as a crucial factor in the regulation of podosome turnover and function. ..
- Shin J, Swift J, Spinler K, Discher D. Myosin-II inhibition and soft 2D matrix maximize multinucleation and cellular projections typical of platelet-producing megakaryocytes. Proc Natl Acad Sci U S A. 2011;108:11458-63 pubmed publisher..Myosin-II thus seems a central, matrix-regulated node for MK-poiesis and platelet generation...
- Dahan I, Yearim A, Touboul Y, Ravid S. The tumor suppressor Lgl1 regulates NMII-A cellular distribution and focal adhesion morphology to optimize cell migration. Mol Biol Cell. 2012;23:591-601 pubmed publisher..Collectively these findings indicate that Lgl1 regulates the polarity of migrating cells by controlling the assembly state of NMII-A, its cellular localization, and focal adhesion assembly. ..
- Heath K, Campos Barros A, Toren A, Rozenfeld Granot G, Carlsson L, Savige J, et al. Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes. Am J Hum Genet. 2001;69:1033-45 pubmed..On the basis of our genetic analyses, the name "MYHIIA syndrome" is proposed to encompass all of these disorders...
- Smutny M, Wu S, Gomez G, Mangold S, Yap A, Hamilton N. Multicomponent analysis of junctional movements regulated by myosin II isoforms at the epithelial zonula adherens. PLoS ONE. 2011;6:e22458 pubmed publisher..This extends our recent analysis of Myosin II at the ZA to demonstrate that Myosin IIA and Myosin IIB make distinct contributions to junctional movement at the ZA...
- Franke J, Dong F, Rickoll W, Kelley M, Kiehart D. Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly. Blood. 2005;105:161-9 pubmed..Further, the application of these methods to biochemically characterize rod mutations could be extended to other myosins responsible for disease. ..
- Meshel A, Wei Q, Adelstein R, Sheetz M. Basic mechanism of three-dimensional collagen fibre transport by fibroblasts. Nat Cell Biol. 2005;7:157-64 pubmed..Thus, we suggest that cyclic myosin II-B assembly and contraction in lamellipodia power 3D fibre movements. ..
- van Leeuwen H, Elliott G, O Hare P. Evidence of a role for nonmuscle myosin II in herpes simplex virus type 1 egress. J Virol. 2002;76:3471-81 pubmed
- Rey M, Valenzuela Fernandez A, Urzainqui A, Yanez Mo M, Perez Martinez M, Penela P, et al. Myosin IIA is involved in the endocytosis of CXCR4 induced by SDF-1alpha. J Cell Sci. 2007;120:1126-33 pubmed
- Smutny M, Cox H, Leerberg J, Kovacs E, Conti M, Ferguson C, et al. Myosin II isoforms identify distinct functional modules that support integrity of the epithelial zonula adherens. Nat Cell Biol. 2010;12:696-702 pubmed publisher..We propose that these two isoform-based modules cooperate to coordinate adhesion receptor and F-actin organization to form apical cadherin junctions. ..
- Diensthuber R, Müller M, Heissler S, Taft M, Chizhov I, Manstein D. Phalloidin perturbs the interaction of human non-muscle myosin isoforms 2A and 2C1 with F-actin. FEBS Lett. 2011;585:767-71 pubmed publisher..In contrast, phalloidin binding to F-actin does not affect the interaction with human non-muscle myosin isoform 2B and Dictyostelium myosin-2 and myosin-5b. ..
- Ilani T, Vasiliver Shamis G, Vardhana S, Bretscher A, Dustin M. T cell antigen receptor signaling and immunological synapse stability require myosin IIA. Nat Immunol. 2009;10:531-9 pubmed publisher..Thus, T cell antigen receptor signaling and the subsequent formation of immunological synapses are active processes dependent on myosin IIA. ..
- Masedunskas A, Sramkova M, Parente L, Sales K, Amornphimoltham P, Bugge T, et al. Role for the actomyosin complex in regulated exocytosis revealed by intravital microscopy. Proc Natl Acad Sci U S A. 2011;108:13552-7 pubmed publisher..Our results provide information on the machinery controlling regulated secretion and show that intravital microscopy provides unique opportunities to address fundamental questions in cell biology under physiological conditions. ..
- Saitoh T, Takemura S, Ueda K, Hosoya H, Nagayama M, Haga H, et al. Differential localization of non-muscle myosin II isoforms and phosphorylated regulatory light chains in human MRC-5 fibroblasts. FEBS Lett. 2001;509:365-9 pubmed..Our results suggest that myosin IIA may be highly activated by diphosphorylation of RLCs and primarily involved in cell migration. ..
- Kovacs M, Wang F, Hu A, Zhang Y, Sellers J. Functional divergence of human cytoplasmic myosin II: kinetic characterization of the non-muscle IIA isoform. J Biol Chem. 2003;278:38132-40 pubmed..Non-muscle myosin II isoforms thus appear to have distinct enzymatic properties that may be of importance in carrying out their cellular functions. ..
- Papeta N, Kiryluk K, Patel A, Sterken R, Kacak N, Snyder H, et al. APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy. J Am Soc Nephrol. 2011;22:1991-6 pubmed publisher..These data further support the strong association of genetic variants in APOL1 with susceptibility to FSGS and HIVAN among African Americans. ..
- Zhang S, Wang G, Liu D, Bao Z, Fernig D, Rudland P, et al. The C-terminal region of S100A4 is important for its metastasis-inducing properties. Oncogene. 2005;24:4401-11 pubmed..The results suggest that the ability to interact with protein target(s) is important in S100A4-induced metastasis. ..
- Seri M, Pecci A, Di Bari F, Cusano R, Savino M, Panza E, et al. MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore). 2003;82:203-15 pubmed..For this new nosologic entity, we propose the term "MHY9-related disease," which better interprets the recent knowledge in this field and identifies all patients at risk of developing renal, hearing, or visual defects. ..
- Betapudi V, Licate L, Egelhoff T. Distinct roles of nonmuscle myosin II isoforms in the regulation of MDA-MB-231 breast cancer cell spreading and migration. Cancer Res. 2006;66:4725-33 pubmed..These results indicate that both isoforms are critical for the mechanics of cell migration, with myosin IIB seeming to have a preferential role in the mechanics of lamellar protrusion. ..
- Bao J, Ma X, Liu C, Adelstein R. Replacement of nonmuscle myosin II-B with II-A rescues brain but not cardiac defects in mice. J Biol Chem. 2007;282:22102-11 pubmed..Thus, although NMHC II-A can substitute for NMHC II-B to maintain integrity of the spinal canal, NMHC II-B plays an isoform-specific role during cytokinesis in cardiac myocytes and in migration of the facial and pontine neurons. ..
- Jacobelli J, Bennett F, Pandurangi P, Tooley A, Krummel M. Myosin-IIA and ICAM-1 regulate the interchange between two distinct modes of T cell migration. J Immunol. 2009;182:2041-50 pubmed publisher..This can provide T lymphocytes with motile and adhesive properties that are uniquely suited toward alternative requirements for immune surveillance and response. ..
- Clark K, Middelbeek J, Dorovkov M, Figdor C, Ryazanov A, Lasonder E, et al. The alpha-kinases TRPM6 and TRPM7, but not eEF-2 kinase, phosphorylate the assembly domain of myosin IIA, IIB and IIC. FEBS Lett. 2008;582:2993-7 pubmed publisher..In conclusion, TRPM6 and TRPM7 share exogenous substrates among themselves but not with functionally distant alpha-kinases. ..
- Somlyo A, Somlyo A. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev. 2003;83:1325-58 pubmed..It is a potentially important therapeutic target and a subject for translational research. ..
- Chen Z, Naveiras O, Balduini A, Mammoto A, Conti M, Adelstein R, et al. The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway. Blood. 2007;110:171-9 pubmed..The unexpected mechanism for Myh9-associated thrombocytopenia may lead to new molecular approaches to manipulate thrombopoiesis. ..
- Clark K, Middelbeek J, Lasonder E, Dulyaninova N, Morrice N, Ryazanov A, et al. TRPM7 regulates myosin IIA filament stability and protein localization by heavy chain phosphorylation. J Mol Biol. 2008;378:790-803 pubmed publisher..In conclusion, our data demonstrate that TRPM7 regulates myosin IIA filament stability and localization by phosphorylating a short stretch of amino acids within the alpha-helical tail of the myosin IIA heavy chain. ..
- Kovacs M, Thirumurugan K, Knight P, Sellers J. Load-dependent mechanism of nonmuscle myosin 2. Proc Natl Acad Sci U S A. 2007;104:9994-9 pubmed..Whereas forward load accelerates the cycle of interaction with actin, resistive load increases duty ratio to favor tension maintenance by two-headed attachment. ..
- Dulyaninova N, Malashkevich V, Almo S, Bresnick A. Regulation of myosin-IIA assembly and Mts1 binding by heavy chain phosphorylation. Biochemistry. 2005;44:6867-76 pubmed
- Kolega J. Asymmetric distribution of myosin IIB in migrating endothelial cells is regulated by a rho-dependent kinase and contributes to tail retraction. Mol Biol Cell. 2003;14:4745-57 pubmed..Blocking this pathway inhibited tail constriction and retraction, but did not affect protrusion, suggesting that myosin IIB functions in pulling the rear of the cell forward. ..
- Zhang Y, Conti M, Malide D, Dong F, Wang A, Shmist Y, et al. Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A. Blood. 2012;119:238-50 pubmed publisher..Our results show that heterozygous mice with mutations in the myosin motor or filament-forming domain manifest similar hematologic, eye, and kidney phenotypes to humans with MYH9-related disease...
- Togo T, Steinhardt R. Nonmuscle myosin IIA and IIB have distinct functions in the exocytosis-dependent process of cell membrane repair. Mol Biol Cell. 2004;15:688-95 pubmed..Myosin IIB was primarily at the subplasmalemma cortex and myosin IIA was concentrated at the trans-Golgi network consistent with their distinct roles in vesicle trafficking in cell membrane repair. ..
- Choi C, Vicente Manzanares M, Zareno J, Whitmore L, Mogilner A, Horwitz A. Actin and alpha-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner. Nat Cell Biol. 2008;10:1039-50 pubmed publisher..From these studies, we have developed a model for adhesion assembly that clarifies the relative contributions of myosin II and actin polymerization and organization. ..
- Delorme Walker V, Peterson J, Chernoff J, Waterman C, Danuser G, DerMardirossian C, et al. Pak1 regulates focal adhesion strength, myosin IIA distribution, and actin dynamics to optimize cell migration. J Cell Biol. 2011;193:1289-303 pubmed publisher..These findings establish Paks as critical molecules coordinating cytoskeletal systems for efficient cell migration...
- Shewan A, Maddugoda M, Kraemer A, Stehbens S, Verma S, Kovacs E, et al. Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts. Mol Biol Cell. 2005;16:4531-42 pubmed..We propose that Myosin 2 is a key effector of Rho-Rho kinase signaling that regulates cell-cell adhesion by determining the ability of cells to concentrate cadherins at contacts in response to homophilic ligation. ..
- Sakamoto T, Limouze J, Combs C, Straight A, Sellers J. Blebbistatin, a myosin II inhibitor, is photoinactivated by blue light. Biochemistry. 2005;44:584-8 pubmed..This property may be useful in locally reversing the action of blebbistatin treatment in a cell. However, caution should be exercised as free radicals may be produced upon irradiation of blebbistatin that could result in cell damage. ..
- Vicente Manzanares M, Zareno J, Whitmore L, Choi C, Horwitz A. Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cells. J Cell Biol. 2007;176:573-80 pubmed..It mediates each of the major component processes that drive migration, e.g., polarization, protrusion, adhesion assembly and turnover, polarity, signaling, and tail retraction, and it integrates spatially separated processes. ..
- Conti M, Even Ram S, Liu C, Yamada K, Adelstein R. Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice. J Biol Chem. 2004;279:41263-6 pubmed..Our results suggest an essential role for a single, specific nonmuscle myosin isoform in maintaining cell-cell adhesions in the early mammalian embryo. ..
- Arora P, Conti M, Ravid S, Sacks D, Kapus A, Adelstein R, et al. Rap1 activation in collagen phagocytosis is dependent on nonmuscle myosin II-A. Mol Biol Cell. 2008;19:5032-46 pubmed publisher..We conclude that MLC phosphorylation in response to initial collagen-bead binding promotes NM II-A filament assembly; binding of Rap1 to myosin filaments enables Rap1-dependent integrin activation and enhanced collagen phagocytosis. ..
- Cai Y, Biais N, Giannone G, Tanase M, Jiang G, Hofman J, et al. Nonmuscle myosin IIA-dependent force inhibits cell spreading and drives F-actin flow. Biophys J. 2006;91:3907-20 pubmed..Our results suggest that NMM-IIA is involved in generating a coherent cytoplasmic contractile force from one side of the cell to the other through the cross-linking and the contraction of dorsal actin filaments. ..
- Even Ram S, Doyle A, Conti M, Matsumoto K, Adelstein R, Yamada K. Myosin IIA regulates cell motility and actomyosin-microtubule crosstalk. Nat Cell Biol. 2007;9:299-309 pubmed..We conclude that myosin IIA negatively regulates cell migration and suggest that it maintains a balance between the actomyosin and microtubule systems by regulating microtubule dynamics. ..
- Arii J, Goto H, Suenaga T, Oyama M, Kozuka Hata H, Imai T, et al. Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1. Nature. 2010;467:859-62 pubmed publisher..The identification of NMHC-IIA as an HSV-1 entry receptor and the involvement of NM-IIA regulation in HSV-1 infection provide an insight into HSV-1 entry and identify new targets for antiviral drug development. ..
- Wang A, Ma X, Conti M, Adelstein R. Distinct and redundant roles of the non-muscle myosin II isoforms and functional domains. Biochem Soc Trans. 2011;39:1131-5 pubmed publisher..However, we also show that certain functions, such as neuronal cell migration in the developing brain and vascularization of the mouse embryo and placenta, specifically require NM II-B and II-A respectively. ..
- Malashkevich V, Dulyaninova N, Ramagopal U, Liriano M, Varney K, Knight D, et al. Phenothiazines inhibit S100A4 function by inducing protein oligomerization. Proc Natl Acad Sci U S A. 2010;107:8605-10 pubmed publisher..Together these studies support a unique mode of inhibition in which phenothiazines disrupt the S100A4/myosin-IIA interaction by sequestering S100A4 via small molecule-induced oligomerization. ..
- Malashkevich V, Varney K, Garrett S, Wilder P, Knight D, Charpentier T, et al. Structure of Ca2+-bound S100A4 and its interaction with peptides derived from nonmuscle myosin-IIA. Biochemistry. 2008;47:5111-26 pubmed publisher..These studies provide the foundation for understanding S100A4 target recognition and may support the development of reagents that interfere with S100A4 function. ..
- Kiss B, Duelli A, Radnai L, Kekesi K, Katona G, Nyitray L. Crystal structure of the S100A4-nonmuscle myosin IIA tail fragment complex reveals an asymmetric target binding mechanism. Proc Natl Acad Sci U S A. 2012;109:6048-53 pubmed publisher..The description of the complex will facilitate the design of specific drugs that interfere with the S100A4-NMIIA interaction. ..
- Li Z, Bresnick A. The S100A4 metastasis factor regulates cellular motility via a direct interaction with myosin-IIA. Cancer Res. 2006;66:5173-80 pubmed..Our studies show for the first time that S100A4 promotes directional motility via a direct interaction with myosin-IIA. These findings establish S100A4 as a critical regulator of myosin-II function and metastasis-associated motility. ..
- Manes T, Pober J. TCR-driven transendothelial migration of human effector memory CD4 T cells involves Vav, Rac, and myosin IIA. J Immunol. 2013;190:3079-88 pubmed publisher..The differential use of small Rho family GTPases to activate the cytoskeleton is consistent with the morphological differences observed in T cells that undergo TEM in response to these distinct recruitment signals. ..