Plectin stabilizes microtubules during osteoclastic bone resorption by acting as a scaffold for Src and Pyk2
Plectin stabilizes microtubules during osteoclastic bone resorption by acting as a scaffold for Src and Pyk2
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Plectin通过作为Src和Pyk 2的支架在骨细胞骨吸收期间稳定微管
DOI：
10.1016/j.bone.2019.115209
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发表时间：
2020-03-01
期刊：
影响因子：
4.1
通讯作者：
Kokabu, Shoichiro
中科院分区：
文献类型：
--
作者：
Matsubara, Takuma;Yaginuma, Tatsuki;Kokabu, Shoichiro
破骨细胞是一种多核细胞，通过吸收骨来维持骨稳态。在骨吸收过程中，破骨细胞通过肌动蛋白环形成的封闭区附着在骨基质上。劳斯肉瘤癌基因（Src）对肌动蛋白环的形成和骨吸收至关重要。最近，我们证明了细胞连接蛋白plectin在破骨细胞中是一种src结合蛋白。然而，粘连素在破骨细胞中的作用尚不清楚。在这项研究中，我们证明了在RAW 264.7细胞中shRNA敲低plectin导致酒石酸盐抗性酸性磷酸酶阳性多核细胞（TRAP (+) MNCs）的肌动蛋白环形成和骨吸收活性受损。此外，我们发现在凝集素沉默的TRAP（+）跨国公司中，Src和蛋白酪氨酸激酶2 β (Pyk2)这两个破骨细胞骨吸收的关键激酶失活，微管极性受到干扰。这些结果表明，在微管组织过程中，plectin作为支架促进Src和Pyk2的激活，在破骨细胞生物学中起着至关重要的作用。
Osteoclasts are multinuclear cells which maintain bone homeostasis by resorbing bone. During bone resorption, osteoclasts attach to the bone matrix via a sealing zone formed by an actin ring. Rous sarcoma oncogene (Src) is essential for actin ring formation and bone resorption. Recently, we demonstrated that plectin, a cytolinker protein, is a Src-binding protein in osteoclasts. However, the function of plectin in osteoclasts remains unknown. In this study, we demonstrated that shRNA knockdown of plectin in RAW 264.7 cells resulted in tartrate resistant acid phosphatase positive multinuclear cells (TRAP (+) MNCs) with impaired actin ring formation and bone resorption activity. Moreover, we found that in plectin-silenced TRAP (+) MNCs, Src and protein tyrosine kinase 2 beta (Pyk2), two critical kinases in osteoclastic bone resorption, were inactivated and microtubule polarity was disturbed. These results suggest that plectin plays a critical role in osteoclast biology by acting as a scaffold to facilitate Src and Pyk2 activation during microtubule organization.