Functional complementation of V-ATPase a subunit isoforms in osteoclasts
Functional complementation of V-ATPase a subunit isoforms in osteoclasts
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DOI：
10.1093/jb/mvaa118
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发表时间：
2021-04-01
影响因子：
2.7
通讯作者：
Nakanishi-Matsui, Mayumi
中科院分区：
文献类型：
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作者：
Matsumoto, Naomi;Sekiya, Mizuki;Nakanishi-Matsui, Mayumi
在破骨细胞中，质子泵送v - atp酶的a3亚型在骨吸收所需的分泌溶酶体的顺行运输和细胞外酸化中起着至关重要的作用。本研究通过在a3敲除（KO）破骨细胞中外源表达a1、a2和a3亚型来检测a亚型的功能互补。a1和a2在a3KO破骨细胞中的表达水平相似，但低于a3。A1明显定位于溶酶体，而a2则略微定位于溶酶体。另一方面，a2与Rab7相互作用，Rab7是破骨细胞分泌溶酶体运输的调节因子，比a1更有效。A1部分补充a3在分泌性溶酶体运输和磷酸钙再吸收中的功能，a2部分补充前者，但不补充后者。
In osteoclasts, the a3 isoform of the proton-pumping V-ATPase plays essential roles in anterograde trafficking of secretory lysosomes and extracellular acidification required for bone resorption. This study examined functional complementation of the a isoforms by exogenously expressing the a1, a2 and a3 isoforms in a3-knockout (KO) osteoclasts. The expression levels of a1 and a2 in a3KO osteoclasts were similar, but lower than that of a3. a1 significantly localized to lysosomes, whereas a2 slightly did. On the other hand, a2 interacted with Rab7, a regulator of secretory lysosome trafficking in osteoclasts, more efficiently than a1. a1 partly complemented the functions of a3 in secretory lysosome trafficking and calcium phosphate resorption, while a2 partly complemented the former but not the latter function.