Genetic suppression of a phosphomimic myosin II identifies system-level factors that promote myosin II cleavage furrow accumulation.
Bottom Line: How myosin II localizes to the cleavage furrow in Dictyostelium and metazoan cells remains largely unknown despite significant advances in understanding its regulation.Finally, an engineered myosin II with a longer lever arm (2xELC), producing a highly mechanosensitive motor, could also partially suppress the intragenic 3xAsp.Overall, myosin II accumulation is the result of multiple parallel and partially redundant pathways that comprise a cellular contractility control system.
Affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.Show MeSH
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Mentions: Mechanosensing provides an important mechanism for directing the localization of myosin II and is fundamental to a wide range of cellular and tissue functions (Engler et al., 2006; Luo and Robinson, 2011). We have shown that mechanosensitive accumulation plays a central role in tuning the cleavage furrow concentration of myosin II (Kee et al., 2012; Figure 8). This myosin mechanosensitive accumulation is performed by a three-part sensor, including force amplification through the myosin II lever arm, myosin BTF assembly/disassembly dynamics, and actin filament anchoring by cortexillin I (Ren et al., 2009). Multiscale modeling elucidates how myosin II force sensing and cooperative actin binding couple to myosin II BTF assembly (Luo et al., 2012), and this coupling is further demonstrated by the ability of 2xELC-3xAsp to accumulate at the cleavage furrow. This model quantitatively accounts for the amounts and kinetics of myosin II accumulation in response to applied stresses. However, this mechanosensory system is only part of a larger control system that tunes the total level of myosin II accumulation at the cleavage furrow under diverse mechanical constraints (Kee et al., 2012). In this control system (Figure 8), cortexillin I not only anchors the actin filaments, but it also links to signal transduction proteins (Faix et al., 1998; Mondal et al., 2010). These signaling proteins, including IQGAPs and the chromosomal passenger complex proteins, then reinforce signals that emanate from the mitotic spindle to direct myosin II accumulation. Overall this control system demonstrates that to decipher the recruitment pathways, these redundant systems must be taken into account.
Affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.