New mechanisms of contractile protein non-muscle myosin II regulation: role of microtubules and tropomyosins the control of the cell contractility
Gloria Asensio Juárez
Centro de Investigación del Cáncer. Universidad de Salamanca - CSIC
The generation of mechanical forces is a fundamental process in biology, controlling biological processes such as homeostasis and tissue morphogenesis, cell migration and division.
The cytoskeleton is a dynamic and adaptive intracellular network comprising three main systems: microfilaments, microtubules, and intermediate filaments. Each of these systems possesses specific dynamic and mechanical properties and functions. Collectively, these systems enable dynamic cellular processes by providing structure, support, organization, and force generation. Whereas the forces necessary for chromosomal segregation during mitosis emanate from dyneins and kinesins, class II myosins produce forces associated to actin filaments. Class II myosins bind to actin and generate contraction through ATP hydrolysis, forming polymers that exert forces through the coordinated movement of actin filaments. Non-muscle myosin II (NMII) has three paralogs: NMII-A, NMII-B and NMII-C. These paralogs have common and specific functions in cell polarization, migration, and division.
This work has two parts. First, we examine the cross-talk between microtubules and actomyosin when the former are inhibited with paclitaxel, a chemotherapeutic agent that impedes cell division and remains in clinical use despite the frequent onset of resistance. We demonstrate that paclitaxel produces actin-dependent contraction through its action on myosin II. In the second part, we address the specific roles of myosin II paralogs in cell adhesion and migration and uncover specific roles for the paralogs in their reciprocal regulation, as well as unexpected roles for non-contractile, tropomyosin-mediated cross-linking in adhesion dynamics.