Department of Physiology and Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Physiology and Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Biol Chem. 2024 Aug;300(8):107539. doi: 10.1016/j.jbc.2024.107539. Epub 2024 Jul 4.
Force generation and motility by actomyosin in nonmuscle cells are spatially regulated by ∼40 tropomyosin (Tpm) isoforms. The means by which Tpms are targeted to specific cellular regions and the mechanisms that result in differential activity of myosin paralogs are unknown. We show that Tpm3.1 and Tpm1.7 inhibit Myosin-IC (Myo1C), with Tpm1.7 more effectively reducing the number of gliding filaments than Tpm3.1. Strikingly, cosedimentation and fluorescence microscopy assays revealed that Tpm3.1 is displaced from actin by Myo1C and not by myosin-II. In contrast, Tpm1.7 is only weakly displaced by Myo1C. Unlike other characterized myosins, Myo1C motility is inhibited by Tpm when the Tpm-actin filament is activated by myosin-II. These results point to a mechanism for the exclusion of myosin-I paralogs from cellular Tpm-decorated actin filaments that are activated by other myosins. Additionally, our results suggest a potential mechanism for myosin-induced Tpm sorting in cells.
肌球蛋白在非肌肉细胞中产生力和运动，这一过程受到大约 40 种肌球蛋白轻链（Tpm）异构体的空间调节。Tpm 被靶向到特定细胞区域的方式以及导致肌球蛋白同工酶活性差异的机制尚不清楚。我们发现 Tpm3.1 和 Tpm1.7 抑制肌球蛋白-IC（Myo1C），其中 Tpm1.7 比 Tpm3.1 更有效地减少滑行丝的数量。引人注目的是，共沉淀和荧光显微镜分析表明，Myo1C 将 Tpm3.1 从肌动蛋白上置换下来，而不是肌球蛋白-II。相比之下，Myo1C 对 Tpm1.7 的置换作用很弱。与其他已鉴定的肌球蛋白不同，当 Tpm-肌动蛋白丝被肌球蛋白-II 激活时，Tpm 会抑制 Myo1C 的运动。这些结果为肌球蛋白-I 同工酶被其他肌球蛋白激活的细胞 Tpm 修饰的肌动蛋白丝所排斥的机制提供了线索。此外，我们的结果还为肌球蛋白诱导 Tpm 分选提供了一种潜在的细胞内机制。
