α-Catenin-mediated cadherin clustering couples cadherin and actin dynamics.
α-Catenin-mediated cadherin clustering couples cadherin and actin dynamics.
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DOI：
10.1083/jcb.201412064
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发表时间：
2015-08-17
期刊：
影响因子：
--
通讯作者：
Troyanovsky SM
中科院分区：
文献类型：
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作者：
Chen CS;Hong S;Indra I;Sergeeva AP;Troyanovsky RB;Shapiro L;Honig B;Troyanovsky SM
α-连环蛋白的肌动蛋白结合域直接与粘附连接中的肌动蛋白相互作用，并可能通过形成与肌动蛋白皮质结合的瞬时钙粘蛋白簇来控制连接的强度和动力学。α-catenin的肌动蛋白结合结构域αABD的功能，包括其在钙粘蛋白-catenin复合物直接锚定到肌动蛋白细胞骨架中的可能作用，仍然不确定。我们在αABD表面发现了两个干扰αABD与肌动蛋白结合的点突变，并利用它们来探测α-连环蛋白-肌动蛋白相互作用在粘附连接中的作用。我们发现，通过αABD直接结合肌动蛋白的连接比通过黏着斑蛋白间接结合肌动蛋白的连接更动态，并且重组αABD与皮质肌动蛋白相互作用，但不与肌动蛋白束相互作用。这种相互作用导致形成许多短寿命的皮质结合αABD簇。我们的数据表明，αABD集群驱动的连续装配的瞬时，肌动蛋白相关的钙粘蛋白-连环蛋白集群的解体是由肌动蛋白解聚。因此，这种肌动蛋白依赖性αABD簇集是一种独特的分子机制，介导通过弱顺式和反式钙粘蛋白相互作用形成的细胞-细胞粘附界面的完整性和重新组装。
The actin-binding domain of α-catenin directly interacts with actin in adherens junctions and may control the junction’s strength and dynamics by forming transient cadherin clusters bound to the actin cortex. The function of the actin-binding domain of α-catenin, αABD, including its possible role in the direct anchorage of the cadherin–catenin complex to the actin cytoskeleton, has remained uncertain. We identified two point mutations on the αABD surface that interfere with αABD binding to actin and used them to probe the role of α-catenin–actin interactions in adherens junctions. We found that the junctions directly bound to actin via αABD were more dynamic than the junctions bound to actin indirectly through vinculin and that recombinant αABD interacted with cortical actin but not with actin bundles. This interaction resulted in the formation of numerous short-lived cortex-bound αABD clusters. Our data suggest that αABD clustering drives the continuous assembly of transient, actin-associated cadherin–catenin clusters whose disassembly is maintained by actin depolymerization. It appears then that such actin-dependent αABD clustering is a unique molecular mechanism mediating both integrity and reassembly of the cell–cell adhesive interface formed through weak cis- and trans-intercadherin interactions.