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Non-muscle myosin II takes centre stage in cell adhesion and migration

Nature Reviews Molecular Cell Biology volume 10, pages 778–790 (2009)Cite this article

Key Points

  • Non-muscle myosin II (NM II) is a hexameric actin-binding protein that is formed of two heavy chains, two essential light chains and two regulatory light chains. Its conformation and function are controlled by phosphorylation of the regulatory light chains and self-assembly into myosin filaments.

  • NM II heavy chains interact through their coiled-coil domains and contain actin-binding and ATPase activities in their head domains. The essential light chains stabilize myosin structure and the regulatory light chains regulate the ATPase activity of NM II.

  • There are three NM II heavy chain isoforms in mammals. These determine the NM II isoforms (NM IIA, NM IIB and NM IIC), which have unique kinetic properties and both specific and overlapping cellular functions.

  • NM II controls cell protrusion, adhesion and polarity through its actin cross-linking and contractile properties. The three isoforms control different aspects of these processes.

  • Myosin activation is regulated by adhesive signalling, which in turn is regulated by the action of myosin on actin organization and contraction though a poorly characterized feedback loop.

  • There are several monogenic human disease syndromes caused by mutations of NM IIA and NM IIC that impair their enzymatic motor activity and ability to self-assemble.

Abstract

Non-muscle myosin II (NM II) is an actin-binding protein that has actin cross-linking and contractile properties and is regulated by the phosphorylation of its light and heavy chains. The three mammalian NM II isoforms have both overlapping and unique properties. Owing to its position downstream of convergent signalling pathways, NM II is central in the control of cell adhesion, cell migration and tissue architecture. Recent insight into the role of NM II in these processes has been gained from loss-of-function and mutant approaches, methods that quantitatively measure actin and adhesion dynamics and the discovery of NM II mutations that cause monogenic diseases.

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Figure 1: Domain structure of NM II.
Figure 2: Regulation of NM II activation and filament formation.
Figure 3: Multiple roles of NM II in cell migration.
Figure 4: NM II in integrin-mediated adhesion.
Figure 5: Roles of NM II in epithelial cell polarization.

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Acknowledgements

The authors apologize for the numerous studies left out owing to journal limits on the number of references. We thank M. A. Conti and J. R. Sellers (National Heart, Lung and Blood Institute (NHLBI)) for helpful suggestions and critical reading of the manuscript. This work was supported by the US National Institutes of Health (NIH) grant GM23244, the Cell Migration Consortium grant U54-GM064346 (A.R.H.), and the Division of Intramural Research, NHLBI, NIH (R.S.A.).

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Author notes

  1. Robert S. Adelstein and Alan Rick Horwitz: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, 22908, Virginia, USA

    Miguel Vicente-Manzanares & Alan Rick Horwitz

  2. Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, 20892-1583, Maryland, USA

    Xuefei Ma & Robert S. Adelstein

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  1. Miguel Vicente-Manzanares
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Correspondence to Miguel Vicente-Manzanares.

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Glossary

Actin filament

A strand of polymerized globular actin subunits that winds around another strand to form a helix. Actin filaments are one of the three major cytoskeletal elements of a cell, along with microtubules and intermediate filaments.

Integrin

One of a large family of heterodimeric transmembrane proteins that functions as a receptor for ECM or cell adhesion molecules.

Coiled coil

A structural domain that can mediate oligomerization. The myosin coiled-coil rod domain contains two α-helices that twist around each other to form a supercoil.

Tonic contractions

Sustained muscular contractions that develop slowly and show a prolonged phase of relaxation.

Actomyosin filaments

Produced when bipolar myosin filaments interact with polymerized actin filaments to exert tension or produce movement.

Lamellipodium

A 1–2 μm-wide band that is made up of a network of dendritic actin filaments and forms the outer edge of a cell protrusion.

Lamellum

The cell region immediately behind the lamellipodium, characterized by the absence of dendritic actin and the presence of longer, bundled actin filaments and slow retrograde flow.

Blebbistatin

A small-molecule inhibitor with high affinity for myosin II that blocks myosin in an actin-detached state.

Pliability

The mechanical properties of the cellular environment. The environment can show low pliability (that is, be elastic or compliant) or high pliability (that is, be rigid or stiff).

Microtubule-organizing centre

A eukaryotic cell structure from which microtubules emanate. During mitosis, the MTOC organizes the mitotic spindle.

Cadherin

A member of a family of type I transmembrane receptors that mediate cell–cell adhesion through homophilic interactions.

Convergent extension

A phase of gastrulation in which layers of cells intercalate (converge) and become longer (extend). Extension is driven by a rearrangement of the cells of the ventral part of the epithelium, which converge towards the ventral midline.

Fibrillogenesis

A cell-induced reorganization of the surrounding ECM molecules into bundled fibres.

Macrothrombocytopenia

A condition that is characterized by enlarged blood platelets that are approximately the size of red blood cells, are reduced in number and result in prolonged bleeding times.

Haploinsufficiency

A state in which the loss of only one allele of a gene detectably disables the encoded protein's function.

Ectopia cordis

A congenital displacement of the heart outside the thoracic cavity and chest wall.

Omphalocele

A protrusion that occurs at birth, whereby part of the intestine protrudes through a large defect in the abdominal wall at the umbilicus.

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Vicente-Manzanares, M., Ma, X., Adelstein, R. et al. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol 10, 778–790 (2009). https://doi.org/10.1038/nrm2786

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