How does the contractome protein network regulate actomyosin contractility?2018-02-06T10:21:35+00:00

How does the contractome protein network regulate actomyosin contractility?

Non-muscle myosin II isoforms have a similar structure and function to their muscle equivalents. However, their interaction with actin serves to generate cellular forces rather than muscular contraction. During non-muscle actomyosin contractility, non-muscle myosin II uses energy from ATP hydrolysis to slide the actin filament to produce contractile force, and these forces have been implicated in multiple cell functions, such as cell adhesion, establishing cell polarity, and cell migration [1][2]. During cell division, actomyosin contractility regulates forces on the nucleus which affect DNA synthesis and chromatin organization, and is also required for formation and contraction of the mitotic spindle [3][4][5][6].

The varied functions associated with actomyosin contractility require the involvement of many proteins other than actin and myosin. Data mining of the literature has revealed the comprehensive network of proteins that regulate actomyosin contractility, termed the ‘contractome’. A total of 100 contractome proteins were identified, comprising of 97 proteins and 3 cofactors. After organizing these proteins based on their primary function, the three biggest functional groups were serine/threonine phosphorylation regulators, primarily kinases (27 proteins), scaffolding proteins (24 proteins), and regulators of actin dynamics (12 proteins).

Using a protein interaction database to probe the contractome for interactions, researchers have been able to isolate the major features of the network. The Rho family of small GTPases activates serine/threonine kinases, and this activation is propagated by self-phosphorylation. The serine/threonine kinases activate regulators of actin dynamics, myosin phosphatase, and the myosin light chain. The scaffold group of proteins act as connectors, forming a link between actin and myosin. Scaffolding proteins also bind to the serine/threonine kinases, RhoGTPases and its RhoGEF and RhoGAP regulators, and regulate the myosin heavy chain. While the contractome demonstrates the complexity of actomyosin contractility, the initial data also reveals certain common functional processes and regulatory pathways [7].

View All

Latest Findings

Protein Info

References

  1. Aguilar-Cuenca R, Juanes-García A, and Vicente-Manzanares M. Myosin II in mechanotransduction: master and commander of cell migration, morphogenesis, and cancer. Cell. Mol. Life Sci. 2013; 71(3):479-92. [PMID: 23934154]
  2. Vicente-Manzanares M, Ma X, Adelstein RS, and Horwitz AR. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat. Rev. Mol. Cell Biol. 2009; 10(11):778-90. [PMID: 19851336]
  3. Hossain MM, Smith PG, Wu K, and Jin J. Cytoskeletal tension regulates both expression and degradation of h2-calponin in lung alveolar cells. Biochemistry 2006; 45(51):15670-83. [PMID: 17176089]
  4. Kumar A, Maitra A, Sumit M, Ramaswamy S, and Shivashankar GV. Actomyosin contractility rotates the cell nucleus. Sci Rep 2014; 4:3781. [PMID: 24445418]
  5. Ramdas NM, and Shivashankar GV. Cytoskeletal control of nuclear morphology and chromatin organization. J. Mol. Biol. 2014; 427(3):695-706. [PMID: 25281900]
  6. Mendes Pinto I, Rubinstein B, and Li R. Force to divide: structural and mechanical requirements for actomyosin ring contraction. Biophys. J. 2013; 105(3):547-54. [PMID: 23931302]
  7. Zaidel-Bar R, Zhenhuan G, and Luxenburg C. The contractome--a systems view of actomyosin contractility in non-muscle cells. J. Cell. Sci. 2015; 128(12):2209-17. [PMID: 26021351]