Identification of novel MYO18A interaction partners required for myoblast adhesion and muscle integrity.
Identification of novel MYO18A interaction partners required for myoblast adhesion and muscle integrity.
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鉴定成肌细胞粘附和肌肉完整性所需的新型 MYO18A 相互作用伙伴
DOI：
10.1038/srep36768
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发表时间：
2016-11-08
影响因子：
4.6
通讯作者：
Shi DL
中科院分区：
文献类型：
--
作者：
Cao JM;Cheng XN;Li SQ;Heller S;Xu ZG;Shi DL
含有PDZ结构域的非常规肌球蛋白MYO 18 A是斑马鱼发育过程中肌肉完整性所必需的。然而，其在肌纤维中发挥作用的机制尚不清楚。PDZ结构域的存在表明MYO 18 A可能与其他伙伴相互作用以执行肌肉特异性功能。在这里，我们进行了双杂交筛选和免疫共沉淀，以确定MYO 18 A相互作用的蛋白质，并确定p190 RhoGEF和Golgin 45作为MYO 18 A PDZ结构域的新伙伴。我们还鉴定了Lurap 1，它以前被证明与MYO 18 A结合。功能分析表明，类似于myo 18 a，通过吗啉代寡核苷酸敲低ofurap 1、p190 RhoGEF和Golgin 45破坏肌营养不良蛋白在肌膜的定位并产生肌肉损伤。同时敲除myo 18 a与这些基因中的任何一个严重破坏肌纤维的完整性和肌营养不良蛋白的定位，这表明它们可能具有类似的功能，以维持肌纤维的完整性。我们进一步表明，MYO 18 A和它的相互作用的合作伙伴所需的成肌细胞的细胞外基质的粘附，并在成肌细胞中的高尔基体和组织的F-肌动蛋白束的形成。这些发现表明MYO 18 A有可能形成一种多蛋白复合物，将高尔基体与F-actin连接起来，从而在早期发育过程中调节肌肉的完整性和功能。
The unconventional myosin MYO18A that contains a PDZ domain is required for muscle integrity during zebrafish development. However, the mechanism by which it functions in myofibers is not clear. The presence of a PDZ domain suggests that MYO18A may interact with other partners to perform muscle-specific functions. Here we performed double-hybrid screening and co-immunoprecipitation to identify MYO18A-interacting proteins, and have identified p190RhoGEF and Golgin45 as novel partners for the MYO18A PDZ domain. We have also identified Lurap1, which was previously shown to bind MYO18A. Functional analyses indicate that, similarly asmyo18a, knockdown oflurap1, p190RhoGEFandGolgin45by morpholino oligonucleotides disrupts dystrophin localization at the sarcolemma and produces muscle lesions. Simultaneous knockdown ofmyo18awith either of these genes severely disrupts myofiber integrity and dystrophin localization, suggesting that they may function similarly to maintain myofiber integrity. We further show that MYO18A and its interaction partners are required for adhesion of myoblasts to extracellular matrix, and for the formation of the Golgi apparatus and organization of F-actin bundles in myoblast cells. These findings suggest that MYO18A has the potential to form a multiprotein complex that links the Golgi apparatus to F-actin, which regulates muscle integrity and function during early development.
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影响因子：
4.9
作者：
Jackson HE;Ono Y;Wang X;Elworthy S;Cunliffe VT;Ingham PW
通讯作者：
Ingham PW
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Codina M;Li J;Gutiérrez J;Kao JP;Du SJ
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通讯作者：
Rottbauer, Wolfgang
影响因子：
3.5
作者：
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通讯作者：
Blake, DJ
影响因子：
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作者：
Berger, Joachim;Berger, Silke;Currie, Peter D.
通讯作者：
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