Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Neurobiology, Regeneration Next, and Duke Institute for Brain Sciences, Duke University Medical Center, Durham, NC 27710, USA.
Dev Cell. 2020 Dec 7;55(5):574-587.e3. doi: 10.1016/j.devcel.2020.10.020. Epub 2020 Nov 24.
Gap junctions are present in most tissues and play essential roles in various biological processes. However, we know surprisingly little about the molecular mechanisms underlying gap junction formation. Here, we uncover the essential role of a conserved EGF- and laminin-G-domain-containing protein nlr-1/CASPR in the regulation of gap junction formation in multiple tissues across different developmental stages in C. elegans. NLR-1 is located in the gap junction perinexus, a region adjacent to but not overlapping with gap junctions, and forms puncta before the clusters of gap junction channels appear on the membrane. We show that NLR-1 can directly bind to actin to recruit F-actin networks at the gap junction formation plaque, and the formation of F-actin patches plays a critical role in the assembly of gap junction channels. Our findings demonstrate that nlr-1/CASPR acts as an early stage signal for gap junction formation through anchoring of F-actin networks.
间隙连接存在于大多数组织中，在各种生物过程中发挥着重要作用。然而，我们对间隙连接形成的分子机制知之甚少。在这里，我们揭示了保守的 EGF 和层粘连蛋白-G 结构域蛋白 nlr-1/CASPR 在调控线虫不同发育阶段多种组织间隙连接形成中的重要作用。NLR-1 位于间隙连接周质，这是一个紧邻但不与间隙连接重叠的区域，并且在膜上出现间隙连接通道簇之前形成斑点。我们表明，NLR-1 可以直接结合肌动蛋白，在间隙连接形成斑上募集 F-肌动蛋白网络，并且 F-肌动蛋白斑块的形成在间隙连接通道的组装中起着关键作用。我们的发现表明，nlr-1/CASPR 通过锚定 F-肌动蛋白网络作为间隙连接形成的早期信号。
