Myosin motor isoforms direct specification of actomyosin function by tropomyosins.

Myosin motor isoforms direct specification of actomyosin function by tropomyosins.
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肌球蛋白运动亚型直接规范原肌球蛋白的肌动球蛋白功能。

DOI:
10.1002/cm.21213
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发表时间:
2015-03
期刊:
影响因子:
2.9
通讯作者:
Lord, Matthew
Lord, Matthew
中科院分区:
生物学4区
文献类型:
--
作者:
Clayton, Joseph E.;Pollard, Luther W.;Murray, George G.;Lord, Matthew

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肌凝蛋白和原肌凝蛋白代表两种细胞骨架蛋白,它们经常在收缩和运动的细胞过程中与肌动蛋白丝一起工作。虽然原肌球蛋白在横纹肌肌球蛋白ii调节中的特殊作用已被很好地描述,但其在非肌肉肌球蛋白调节中的作用却知之甚少。我们之前的研究表明,裂变酵母原肌球蛋白(Cdc8p)正调控肌球蛋白- ii (Myo2p)和肌球蛋白- v (Myo52p)马达。为了了解这种调控的更广泛意义,我们研究了两种哺乳动物原肌球蛋白(Tpm3.1cy/Tm5NM1和Tpm4.2cy/Tm4)最近在癌细胞增殖和转移中的作用。与Cdc8p一样,Tpm3.1cy和Tpm4.2cy同工型显著增强Myo2p和Myo52p运动活性,将非进程性Myo52p分子转化为可以作为单个分子沿着肌动蛋白轨迹行走的进程性马达。与Myo2p和Myo52p的正调控相反,Cdc8p和哺乳动物原肌球蛋白能有效抑制骨骼肌肌球蛋白- ii,而对高度进展的哺乳动物肌球蛋白- va的影响可以忽略不计。为了支持某些原肌球蛋白在调节非肌肉肌动肌球蛋白结构中的保守作用,Tpm3.1cy支持裂变酵母正常的收缩环功能。我们的研究表明,原肌凝蛋白对肌动球蛋白的调节依赖于肌凝蛋白异构体,强调了原肌凝蛋白特定异构体在肌凝蛋白运动输出分选中的一般作用。
Myosins and tropomyosins represent two cytoskeletal proteins that often work together with actin filaments in contractile and motile cellular processes. While the specialized role of tropomyosin in striated muscle myosin-II regulation is well characterized, its role in non-muscle myosin regulation is poorly understood. We previously showed that fission yeast tropomyosin (Cdc8p) positively regulates myosin-II (Myo2p) and myosin-V (Myo52p) motors. To understand the broader implications of this regulation we examined the role of two mammalian tropomyosins (Tpm3.1cy/Tm5NM1 and Tpm4.2cy/Tm4) recently implicated in cancer cell proliferation and metastasis. Like Cdc8p, the Tpm3.1cy and Tpm4.2cy isoforms significantly enhance Myo2p and Myo52p motor activity, converting non-processive Myo52p molecules into processive motors that can walk along actin tracks as single molecules. In contrast to the positive regulation of Myo2p and Myo52p, Cdc8p and the mammalian tropomyosins potently inhibited skeletal muscle myosin-II, while having negligible effects on the highly processive mammalian myosin-Va. In support of a conserved role for certain tropomyosins in regulating non-muscle actomyosin structures, Tpm3.1cy supported normal contractile ring function in fission yeast. Our work reveals that actomyosin regulation by tropomyosin is dependent on the myosin isoform, highlighting a general role for specific isoforms of tropomyosin in sorting myosin motor outputs.
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