Key result
Genetic suppression of a phosphomimic myosin II mutant identified multiple genes, including RMD1, that promote myosin II cleavage furrow accumulation and rescue cytokinesis defects.
Myosin II accumulation at the cleavage furrow is controlled by multiple parallel and partially redundant pathways, including chemical signaling and mechanical stress.
Reveals redundant pathways for myosin II localization in cytokinesis; leaves open relevance to mammalian cardiac cells or disease.
How myosin II localizes to the cleavage furrow in Dictyostelium and metazoan cells remains largely unknown despite significant advances in understanding its regulation. We designed a genetic selection using cDNA library suppression of 3xAsp myosin II to identify factors involved in myosin cleavage furrow accumulation. The 3xAsp mutant is deficient in bipolar thick filament assembly, fails to accumulate at the cleavage furrow, cannot rescue myoII-null cytokinesis, and has impaired mechanosensitive accumulation. Eleven genes suppressed this dominant cytokinesis deficiency when 3xAsp was expressed in wild-type cells. 3xAsp myosin II's localization to the cleavage furrow was rescued by constructs encoding rcdBB, mmsdh, RMD1, actin, one novel protein, and a 14-3-3 hairpin. Further characterization showed that RMD1 is required for myosin II cleavage furrow accumulation, acting in parallel with mechanical stress. Analysis of several mutant strains revealed that different thresholds of myosin II activity are required for daughter cell symmetry than for furrow ingression dynamics. 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.
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Ren et al. (2014) studied Cytokinesis defects. Genetic suppression of 3xAsp myosin II vs. Empty vector control was evaluated on Myosin II cleavage furrow accumulation (If/Ip ratio). Genetic suppression of a phosphomimic myosin II mutant identified multiple genes, including RMD1, that promote myosin II cleavage furrow accumulation and rescue cytokinesis defects.
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