DRC3 connects the N-DRC to dynein g to regulate flagellar waveform.
DRC3 connects the N-DRC to dynein g to regulate flagellar waveform.
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DRC3将N-DRC连接到Dynein G，以调节鞭毛波形。
DOI：
10.1091/mbc.e15-01-0018
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发表时间：
2015-08-01
影响因子：
3.3
通讯作者：
Witman GB
中科院分区：
文献类型：
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作者：
Awata J;Song K;Lin J;King SM;Sanderson MJ;Nicastro D;Witman GB
连接蛋白-动力蛋白调节复合物（N-DRC）是调节纤毛运动的轴丝结构。缺乏 N-DRC 亚基 DRC3 的衣藻突变体具有异常波形，并且缺乏部分 N-DRC 连接子，包括连接动力蛋白 g 的 L1 突出。 DRC3 与动力蛋白相互作用来控制纤毛波形。连接蛋白-动力蛋白调节复合物 (N-DRC) 是控制鞭毛运动的主要枢纽，包含至少 11 个不同的亚基。一个主要的挑战是确定这些亚基在 N-DRC 内的位置和功能。我们鉴定了 N-DRC 亚基 DRC3 缺陷的衣藻突变体。在已知的 N-DRC 亚基中，drc3 突变体仅缺失 DRC3。与其他 N-DRC 突变体一样，drc3 突变体在鞭毛运动方面存在缺陷。然而，与影响 N-DRC 的其他突变相比，drc3 不会抑制由于径向辐条缺失而引起的鞭毛麻痹。冷冻电子断层扫描显示，drc3 突变体缺乏 N-DRC 连接结构域的一部分，包括 L1 突出、远端叶的一部分以及这两个结构之间的连接，从而将 DRC3 定位于 N-DRC 的这一部分。这个和其他考虑因素使我们能够将 DRC3 分配给 L1 突出。由于 L1 突起是野生型轴丝中与动力蛋白 g 运动结构域接触的唯一非动力蛋白结构，并且这是 drc3 突变体中唯一缺失的 N-DRC-动力蛋白连接，因此我们得出结论，DRC3 与动力蛋白 g 相互作用来调节鞭毛波形。
The nexin-dynein regulatory complex (N-DRC) is an axonemal structure that regulates ciliary motility. A Chlamydomonas mutant lacking the N-DRC subunit DRC3 has abnormal waveform and lacks portions of the N-DRC linker, including the L1 protrusion that connects to dynein g. DRC3 interacts with dynein g to control ciliary waveform. The nexin-dynein regulatory complex (N-DRC), which is a major hub for the control of flagellar motility, contains at least 11 different subunits. A major challenge is to determine the location and function of each of these subunits within the N-DRC. We characterized a Chlamydomonas mutant defective in the N-DRC subunit DRC3. Of the known N-DRC subunits, the drc3 mutant is missing only DRC3. Like other N-DRC mutants, the drc3 mutant has a defect in flagellar motility. However, in contrast to other mutations affecting the N-DRC, drc3 does not suppress flagellar paralysis caused by loss of radial spokes. Cryo–electron tomography revealed that the drc3 mutant lacks a portion of the N-DRC linker domain, including the L1 protrusion, part of the distal lobe, and the connection between these two structures, thus localizing DRC3 to this part of the N-DRC. This and additional considerations enable us to assign DRC3 to the L1 protrusion. Because the L1 protrusion is the only non-dynein structure in contact with the dynein g motor domain in wild-type axonemes and this is the only N-DRC–dynein connection missing in the drc3 mutant, we conclude that DRC3 interacts with dynein g to regulate flagellar waveform.