CRACR2a is a calcium-activated dynein adaptor protein that regulates endocytic traffic.
CRACR2a is a calcium-activated dynein adaptor protein that regulates endocytic traffic.
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CRACR2a 是一种钙激活动力蛋白接头蛋白，可调节内吞流量。
DOI：
10.1083/jcb.201806097
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Vale,RonaldD
中科院分区：
文献类型：
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作者：
Wang,Yuxiao;Huynh,Walter;Skokan,TaylorD;Lu,Wen;Weiss,Arthur;Vale,RonaldD
细胞质动力蛋白是一种负端定向的微管马达，用于运输细胞内的货物。运输由卷曲螺旋接头启动，该接头 (a) 将动力蛋白及其辅因子动力蛋白连接成运动复合物，并且 (b) 与货物结合受体（通常是细胞器上的 Rab GTP 酶）相互作用。在这里，我们报告了两种新型动力蛋白接头 CRACR2a 和 Rab45，它们具有卷曲螺旋接头结构域、一对 EF 手和融合到单个多肽中的 Rab GTPase。在体外，钙激活 CRACR2a 介导的动力蛋白运动，而不是 Rab45 介导的动力蛋白运动。在 Jurkat T 细胞中，细胞内钙的升高会激活 CRACR2a 介导的动力蛋白转运。我们进一步发现，T 细胞受体激活诱导质膜上 CRACR2a 点的形成，该点最初与肌动蛋白皮层结合，随后分离并沿着微管移动，表明存在内吞过程。这些结果提供了 Rab GTPases 的第一个例子，它直接充当动力蛋白接头，并表明 CRACR2a-动力蛋白参与钙调节的内吞运输。
Cytoplasmic dynein is a minus end–directed microtubule motor that transports intracellular cargoes. Transport is initiated by coiled-coil adaptors that (a) join dynein and its cofactor dynactin into a motile complex and (b) interact with a cargo-bound receptor, which is frequently a Rab GTPase on an organelle. Here, we report two novel dynein adaptors, CRACR2a and Rab45, that have a coiled-coil adaptor domain, a pair of EF-hands, and a Rab GTPase fused into a single polypeptide. CRACR2a-mediated, but not Rab45-mediated, dynein motility is activated by calcium in vitro. In Jurkat T cells, elevation of intracellular calcium activates CRACR2a-mediated dynein transport. We further found that T cell receptor activation induces the formation of CRACR2a puncta at the plasma membrane, which initially associate with the actin cortex and subsequently detach and travel along microtubules, suggestive of an endocytic process. These results provide the first examples of Rab GTPases that directly act as dynein adaptors and implicate CRACR2a–dynein in calcium-regulated endocytic trafficking.