nonmuscle myosin type iib


Summary: A nonmuscle isoform of myosin type II found predominantly in neuronal tissue.

Top Publications

  1. Vicente Manzanares M, Koach M, Whitmore L, Lamers M, Horwitz A. Segregation and activation of myosin IIB creates a rear in migrating cells. J Cell Biol. 2008;183:543-54 pubmed publisher
  2. 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. ..
  3. Ma X, Kawamoto S, Uribe J, Adelstein R. Function of the neuron-specific alternatively spliced isoforms of nonmuscle myosin II-B during mouse brain development. Mol Biol Cell. 2006;17:2138-49 pubmed
    ..Some of the B2-ablated Purkinje cells are misplaced in the cerebellar molecular layer. All of the B2-ablated mice demonstrated impaired motor coordination. ..
  4. Kim K, Kovacs M, Kawamoto S, Sellers J, Adelstein R. Disease-associated mutations and alternative splicing alter the enzymatic and motile activity of nonmuscle myosins II-B and II-C. J Biol Chem. 2005;280:22769-75 pubmed
    ..Insertion of eight amino acids into the HMM II-C heavy chain increases both actin-activated MgATPase activity and in vitro motility. ..
  5. Nakahata S, Kawamoto S. Tissue-dependent isoforms of mammalian Fox-1 homologs are associated with tissue-specific splicing activities. Nucleic Acids Res. 2005;33:2078-89 pubmed
    ..These findings suggest that tissue-specific isoforms of Fxh and A2BP1 play an important role in determining tissue specificity of UGCAUG-mediated alternative splicing. ..
  6. 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. ..
  7. Mitsuhashi M, Sakata H, Kinjo M, Yazawa M, Takahashi M. Dynamic assembly properties of nonmuscle myosin II isoforms revealed by combination of fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy. J Biochem. 2011;149:253-63 pubmed publisher
  8. Ma X, Takeda K, Singh A, Yu Z, Zerfas P, Blount A, et al. Conditional ablation of nonmuscle myosin II-B delineates heart defects in adult mice. Circ Res. 2009;105:1102-9 pubmed publisher
    ..We also define a role for NMII-B in maintaining the integrity of intercalated discs. ..
  9. Ma X, Kawamoto S, Hara Y, Adelstein R. A point mutation in the motor domain of nonmuscle myosin II-B impairs migration of distinct groups of neurons. Mol Biol Cell. 2004;15:2568-79 pubmed
    ..These studies demonstrate that NMHC II-B is particularly important for normal migration of distinct groups of neurons during mouse brain development. ..

More Information


  1. 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. ..
  2. Norstrom M, Smithback P, Rock R. Unconventional processive mechanics of non-muscle myosin IIB. J Biol Chem. 2010;285:26326-34 pubmed publisher
    ..However, backward steps are nearly force-independent. Our data support a model in which NMIIB can readily move in both directions at stall, which may be important for a general regulator of cytoskeleton tension. ..
  3. Takeda K, Kishi H, Ma X, Yu Z, Adelstein R. Ablation and mutation of nonmuscle myosin heavy chain II-B results in a defect in cardiac myocyte cytokinesis. Circ Res. 2003;93:330-7 pubmed
    ..Whereas cardiac myocytes completely ablated for NMHC II-B show enlargement and binucleation, mice expressing as little as 6% of the normal amount of wild-type NMHC II-B in the heart do not show these abnormalities. ..
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. 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. ..
  8. Even Faitelson L, Ravid S. PAK1 and aPKCzeta regulate myosin II-B phosphorylation: a novel signaling pathway regulating filament assembly. Mol Biol Cell. 2006;17:2869-81 pubmed
  9. Lo C, Buxton D, Chua G, Dembo M, Adelstein R, Wang Y. Nonmuscle myosin IIb is involved in the guidance of fibroblast migration. Mol Biol Cell. 2004;15:982-9 pubmed
    ..Our results suggest that myosin IIB is involved not in propelling but in directing the cell movement, by coordinating protrusive activities and stabilizing the cell polarity. ..
  10. 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. ..
  11. 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. ..
  12. 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. ..
  13. Sjuve R, Haase H, Ekblad E, Malmqvist U, Morano I, Arner A. Increased expression of non-muscle myosin heavy chain-B in connective tissue cells of hypertrophic rat urinary bladder. Cell Tissue Res. 2001;304:271-8 pubmed
    ..The NM-MHC-B-positive cells could have a role in the production of extracellular matrix and growth factors or be involved in modulation of spontaneous contractile activity. ..
  14. Rubio M, Johnson R, Miller C, Huganir R, Rumbaugh G. Regulation of synapse structure and function by distinct myosin II motors. J Neurosci. 2011;31:1448-60 pubmed publisher
    ..Thus, myosin II motor activity is emerging as a broad regulatory mechanism for control over complex actin networks within dendritic spines. ..
  15. McLachlan R, Yap A. Protein tyrosine phosphatase activity is necessary for E-cadherin-activated Src signaling. Cytoskeleton (Hoboken). 2011;68:32-43 pubmed publisher
    ..We conclude that PTP-activated Src signaling is a possible upstream regulator of myosin IIB at the epithelial zonula adherens...
  16. Ramamurthy B, Yengo C, Straight A, Mitchison T, Sweeney H. Kinetic mechanism of blebbistatin inhibition of nonmuscle myosin IIb. Biochemistry. 2004;43:14832-9 pubmed
    ..These effects are likely mediated by binding of blebbistatin within the myosin cleft that progressively closes in forming the acto-myosin rigor state. ..
  17. Ryu J, Liu L, Wong T, Wu D, Burette A, Weinberg R, et al. A critical role for myosin IIb in dendritic spine morphology and synaptic function. Neuron. 2006;49:175-82 pubmed
    ..Thus, the structure and function of spines is regulated by an actin-based motor in addition to the polymerization state of actin. ..
  18. 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...
  19. Ma X, Jana S, Conti M, Kawamoto S, Claycomb W, Adelstein R. Ablation of nonmuscle myosin II-B and II-C reveals a role for nonmuscle myosin II in cardiac myocyte karyokinesis. Mol Biol Cell. 2010;21:3952-62 pubmed publisher
    ..Our study shows that NM II is involved in regulating cardiac myocyte karyokinesis by affecting microtubule dynamics. ..
  20. Wylie S, Chantler P. Myosin IIC: a third molecular motor driving neuronal dynamics. Mol Biol Cell. 2008;19:3956-68 pubmed publisher
    ..This novel combination of properties suggests that myosin IIC must participate in distinctive cellular roles and reinforces our view that closely related motor isoforms drive diverse functions within neuronal cells. ..
  21. Tullio A, Accili D, Ferrans V, Yu Z, Takeda K, Grinberg A, et al. Nonmuscle myosin II-B is required for normal development of the mouse heart. Proc Natl Acad Sci U S A. 1997;94:12407-12 pubmed
  22. Rosenfeld S, Xing J, Chen L, Sweeney H. Myosin IIb is unconventionally conventional. J Biol Chem. 2003;278:27449-55 pubmed
  23. Hildebrand J. Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network. J Cell Sci. 2005;118:5191-203 pubmed
    ..Thus, Shroom likely facilitates neural tube closure by regulating cell shape changes via the apical positioning of an actomyosin network in the neurepithelium. ..
  24. Even Faitelson L, Rosenberg M, Ravid S. PAK1 regulates myosin II-B phosphorylation, filament assembly, localization and cell chemotaxis. Cell Signal. 2005;17:1137-48 pubmed
    ..Furthermore, the data presented here suggest that PAK1 plays a crucial role in the regulation of cell morphology and chemotaxis by regulating the phosphorylation and cellular localization of myosin II-B. ..
  25. Ma X, Bao J, Adelstein R. Loss of cell adhesion causes hydrocephalus in nonmuscle myosin II-B-ablated and mutated mice. Mol Biol Cell. 2007;18:2305-12 pubmed
    ..These studies show that the scaffolding properties of NM II-B play an important role in cell adhesion, thereby preventing hydrocephalus during mouse brain development. ..
  26. Getty A, Benedict J, Pearce D. A novel interaction of CLN3 with nonmuscle myosin-IIB and defects in cell motility of Cln3(-/-) cells. Exp Cell Res. 2011;317:51-69 pubmed publisher
    ..We propose that the migration defect in Cln3(-/-) results, in part, from the loss of the CLN3-myosin-IIB interaction. ..
  27. Kim K, Kawamoto S, Bao J, Sellers J, Adelstein R. The B2 alternatively spliced isoform of nonmuscle myosin II-B lacks actin-activated MgATPase activity and in vitro motility. Biochem Biophys Res Commun. 2008;369:124-34 pubmed
    ..This indicates that the effect of the II-B2 insert is myosin heavy chain specific. ..
  28. Wang A, Ma X, Conti M, Liu C, Kawamoto S, Adelstein R. Nonmuscle myosin II isoform and domain specificity during early mouse development. Proc Natl Acad Sci U S A. 2010;107:14645-50 pubmed publisher
    ..These results highlight the functions of the N-terminal motor and C-terminal rod domains of NM II and their different roles in cell-cell and cell-matrix adhesion...
  29. Kim K, Adelstein R, Kawamoto S. Identification of neuronal nuclei (NeuN) as Fox-3, a new member of the Fox-1 gene family of splicing factors. J Biol Chem. 2009;284:31052-61 pubmed publisher
    ..Identification of NeuN as Fox-3 clarifies an important element of neurobiology research. ..
  30. Bridgman P, Dave S, Asnes C, Tullio A, Adelstein R. Myosin IIB is required for growth cone motility. J Neurosci. 2001;21:6159-69 pubmed
    ..These activities are essential for growth cone forward advancement, which is necessary for outgrowth. Thus outgrowth is slowed, but not eliminated, in neurons from the myosin IIB KO mice. ..
  31. Swailes N, Colegrave M, Knight P, Peckham M. Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse. J Cell Sci. 2006;119:3561-70 pubmed
  32. Wang F, Kovacs M, Hu A, Limouze J, Harvey E, Sellers J. Kinetic mechanism of non-muscle myosin IIB: functional adaptations for tension generation and maintenance. J Biol Chem. 2003;278:27439-48 pubmed
    ..This feature is even more pronounced at slightly elevated ADP levels, and it may be important in carrying out the cellular functions of this isoform working in small filamentous assemblies. ..
  33. Vicente Manzanares M, Newell Litwa K, Bachir A, Whitmore L, Horwitz A. Myosin IIA/IIB restrict adhesive and protrusive signaling to generate front-back polarity in migrating cells. J Cell Biol. 2011;193:381-96 pubmed publisher
    ..These observations lead to a model for front-back polarity through local GEF depletion. ..
  34. Rex C, Gavin C, Rubio M, Kramar E, Chen L, Jia Y, et al. Myosin IIb regulates actin dynamics during synaptic plasticity and memory formation. Neuron. 2010;67:603-17 pubmed publisher
    ..Our studies provide a mechanical framework for understanding cytoskeletal dynamics associated with synaptic plasticity and memory formation. ..
  35. Bao J, Jana S, Adelstein R. Vertebrate nonmuscle myosin II isoforms rescue small interfering RNA-induced defects in COS-7 cell cytokinesis. J Biol Chem. 2005;280:19594-9 pubmed
  36. Strick D, Feng W, Vollrath D. Mertk drives myosin II redistribution during retinal pigment epithelial phagocytosis. Invest Ophthalmol Vis Sci. 2009;50:2427-35 pubmed publisher
    ..Mertk mobilizes myosin II from the RPE cell periphery to sites of OS engulfment, where myosin II function is essential for the normal phagocytic ingestion of OS. ..
  37. Betapudi V, Rai V, Beach J, Egelhoff T. Novel regulation and dynamics of myosin II activation during epidermal wound responses. Exp Cell Res. 2010;316:980-91 pubmed publisher
  38. Rothermel T, Engelhardt B, Sheibani N. Polyoma virus middle-T-transformed PECAM-1 deficient mouse brain endothelial cells proliferate rapidly in culture and form hemangiomas in mice. J Cell Physiol. 2005;202:230-9 pubmed
  39. Ahuja P, Perriard E, Trimble W, Perriard J, Ehler E. Probing the role of septins in cardiomyocytes. Exp Cell Res. 2006;312:1598-609 pubmed
    ..In addition, we were able to dissect the different contributions of ROCK signaling and the actomyosin cytoskeleton to septin localization to the contractile ring using cardiomyocytes as an experimental system. ..
  40. Bazellieres E, Massey Harroche D, Barthelemy Requin M, Richard F, Arsanto J, Le Bivic A. Apico-basal elongation requires a drebrin-E-EB3 complex in columnar human epithelial cells. J Cell Sci. 2012;125:919-31 pubmed publisher
    ..Taken together, these data suggest that this complex connects the F-actin and microtubule networks apically during epithelial cell morphogenesis, while drebrin E also contributes to stabilizing the actin-based terminal web. ..
  41. Leenders W, Lubsen N, van Altena M, Clauss M, Deckers M, Lowik C, et al. Design of a variant of vascular endothelial growth factor-A (VEGF-A) antagonizing KDR/Flk-1 and Flt-1. Lab Invest. 2002;82:473-81 pubmed
    ..Thus, HD-VEGF blocks KDR- and Flt-1-mediated VEGF activities that are crucial in the angiogenic process and is therefore a promising, multipotent compound in the treatment of angiogenesis-related diseases. ..
  42. Pandorf C, Jiang W, Qin A, Bodell P, Baldwin K, Haddad F. Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2012;302:R854-67 pubmed publisher
    ..The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development. ..
  43. Kiboku T, Katoh T, Nakamura A, Kitamura A, Kinjo M, Murakami Y, et al. Nonmuscle myosin II folds into a 10S form via two portions of tail for dynamic subcellular localization. Genes Cells. 2013;18:90-109 pubmed publisher
    ..These results suggest that the 10S form is necessary for maintaining nonmuscle myosin II in an unassembled state and for recruitment of nonmuscle myosin II to a specific region of the cell. ..
  44. Haque F, Kaku Y, Fujimura S, Ohmori T, Adelstein R, Nishinakamura R. Non-muscle myosin II deletion in the developing kidney causes ureter-bladder misconnection and apical extrusion of the nephric duct lineage epithelia. Dev Biol. 2017;427:121-130 pubmed publisher
    ..Thus, myosin II is essential for maintaining the apicobasal integrity of the developing kidney epithelia independently of Ret signaling. ..
  45. Verdier V, Guang Chao Chen -, Settleman J. Rho-kinase regulates tissue morphogenesis via non-muscle myosin and LIM-kinase during Drosophila development. BMC Dev Biol. 2006;6:38 pubmed
    ..These findings indicate widespread diverse roles for DRok in tissue morphogenesis during Drosophila development, in which multiple DRok substrates appear to be required. ..
  46. Zhao Q, Ishibashi M, Hiasa K, Tan C, Takeshita A, Egashira K. Essential role of vascular endothelial growth factor in angiotensin II-induced vascular inflammation and remodeling. Hypertension. 2004;44:264-70 pubmed
    ..VEGF is an essential mediator in Ang II-induced vascular inflammation and structural changes through its proinflammatory actions. ..
  47. Sibug R, de Koning J, Tijssen A, de Ruiter M, de Kloet E, Helmerhorst F. Urinary gonadotrophins but not recombinant gonadotrophins reduce expression of VEGF120 and its receptors flt-1 and flk-1 in the mouse uterus during the peri-implantation period. Hum Reprod. 2005;20:649-56 pubmed
    ..The CRH system was not affected by the two types of gonadotrophins. ..
  48. Patzak A, Petzhold D, Wronski T, Martinka P, Babu G, Periasamy M, et al. Constriction velocities of renal afferent and efferent arterioles of mice are not related to SMB expression. Kidney Int. 2005;68:2726-34 pubmed
  49. Nii M, Lai J, Keeney M, Han L, Behn A, Imanbayev G, et al. The effects of interactive mechanical and biochemical niche signaling on osteogenic differentiation of adipose-derived stem cells using combinatorial hydrogels. Acta Biomater. 2013;9:5475-83 pubmed publisher
  50. Mousavi K, Parry D, Jasmin B. BDNF rescues myosin heavy chain IIB muscle fibers after neonatal nerve injury. Am J Physiol Cell Physiol. 2004;287:C22-9 pubmed
  51. Manabe I, Kurabayashi M, Shimomura Y, Kuro O M, Watanabe N, Watanabe M, et al. Isolation of the embryonic form of smooth muscle myosin heavy chain (SMemb/NMHC-B) gene and characterization of its 5'-flanking region. Biochem Biophys Res Commun. 1997;239:598-605 pubmed
    ..We conclude that expression of the SMemb/NMHC-B gene is regulated through an interaction between a sequence element located at -100 and a distinct member of CCAAT-binding proteins. ..
  52. Ishmael J, Safic M, Amparan D, Vogel W, Pham T, Marley K, et al. Nonmuscle myosins II-B and Va are components of detergent-resistant membrane skeletons derived from mouse forebrain. Brain Res. 2007;1143:46-59 pubmed
    ..Myosin II-B, however, is more loosely associated with PSD fractions than myosin Va, which appears to be a core PSD protein. ..
  53. Billington N, Wang A, Mao J, Adelstein R, Sellers J. Characterization of three full-length human nonmuscle myosin II paralogs. J Biol Chem. 2013;288:33398-410 pubmed publisher
    ..The data show that although NM IIA and IIB form filaments with similar properties, NM IIC forms filaments that are less well suited to roles such as tension maintenance within the cell...