Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Proc Natl Acad Sci U S A. 2021 Jun 15;118(24). doi: 10.1073/pnas.2023510118.
Cadherins harness the actin cytoskeleton to build cohesive sheets of cells using paradoxically weak bonds, but the molecular mechanisms are poorly understood. In one popular model, actin organizes cadherins into large, micrometer-sized clusters known as puncta. Myosin is thought to pull on these puncta to generate strong adhesion. Here, however, we show that cadherin puncta are actually interdigitated actin microspikes generated by actin polymerization mediated by three factors (Arp2/3, EVL, and CRMP-1). The convoluted membranes in these regions give the impression of cadherin clustering by fluorescence microscopy, but the ratio of cadherin to membrane is constant. Nevertheless, these interlocking fingers of membrane are important for adhesion because perturbing their formation disrupts cell adhesion. In contrast, blocking myosin-dependent contractility does not disrupt either the interdigitated microspikes or lateral membrane adhesion. "Puncta" are zones of strong cell-cell adhesion not due to cadherin clustering but that occur because the interdigitated microspikes expand the surface area available for adhesive bond formation and increase the asperity of the cell surface to promote friction between cells.
钙黏蛋白利用矛盾的弱键将肌动蛋白细胞骨架组装成有凝聚力的细胞片，但分子机制尚不清楚。在一个流行的模型中，肌动蛋白将钙黏蛋白组织成大型的、微米大小的称为斑点的簇。肌球蛋白被认为可以拉动这些斑点来产生强粘附力。然而，在这里，我们发现钙黏蛋白斑点实际上是由肌动蛋白聚合产生的交错的肌动蛋白微刺，这种聚合由三种因子（Arp2/3、EVL 和 CRMP-1）介导。在这些区域中，曲折的膜给人以荧光显微镜下钙黏蛋白聚集的印象，但钙黏蛋白与膜的比例是恒定的。然而，这些交错的膜指对于粘附是很重要的，因为干扰它们的形成会破坏细胞粘附。相比之下，阻止肌球蛋白依赖性收缩性并不会破坏交错的微刺或侧向膜粘附。“斑点”是细胞间强烈粘附的区域，不是由于钙黏蛋白聚集，而是由于交错的微刺扩大了可用于形成粘附结合的表面积，并增加了细胞表面的粗糙度，以促进细胞之间的摩擦。
