N-cadherin association with lipid rafts regulates its dynamic assembly at cell-cell junctions in C2C12 myoblasts
N-cadherin association with lipid rafts regulates its dynamic assembly at cell-cell junctions in C2C12 myoblasts
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DOI：
10.1091/mbc.e04-09-0829
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发表时间：
2005-05-01
影响因子：
3.3
通讯作者：
Gauthier-Rouvière, C
中科院分区：
文献类型：
--
作者：
Causeret, M;Taulet, N;Gauthier-Rouvière, C
钙粘蛋白是一种嗜同性细胞间粘附分子，在胚胎发育过程中参与细胞生长、分化和组织形成。它们聚集在细胞-细胞接触部位，并作为粘附激活的信号受体。在这里，我们表明，在细胞-细胞接触的N-钙粘蛋白的动态组装涉及脂筏。在C2 C12成肌细胞中，免疫荧光和生化实验表明，存在于细胞-细胞接触的N-钙粘蛋白与脂筏共定位。脂筏的破坏导致细胞间粘附的抑制和N-钙粘蛋白依赖性细胞间接触的解体，而不改变N-钙粘蛋白与连环蛋白的结合及其在质膜上的可用性。光漂白实验后的荧光恢复表明，在背质膜，脂筏不直接参与N-钙粘蛋白的扩散流动性。相反，在细胞-细胞连接处，N-钙粘蛋白与脂筏的结合允许其稳定化，从而能够形成功能性粘附复合物。我们发现，脂筏，作为亲同性相互作用和F-肌动蛋白协会，稳定钙粘蛋白依赖的粘附复合物。N-钙粘蛋白与脂筏的结合需要亲脂性相互作用和F-肌动蛋白结合。因此，我们确定脂筏作为钙粘蛋白介导的细胞粘附的新的监管机构。
Cadherins are homophilic cell-cell adhesion molecules implicated in cell growth, differentiation, and organization into tissues during embryonic development. They accumulate at cell-cell contact sites and act as adhesion-activated signaling receptors. Here, we show that the dynamic assembly of N-cadherin at cell-cell contacts involves lipid rafts. In C2C12 myoblasts, immunofluorescence and biochemical experiments demonstrate that N-cadherin present at cell-cell contacts is colocalized with lipid rafts. Disruption of lipid rafts leads to the inhibition of cell-cell adhesion and disorganization of N-cadherin-dependent cell-cell contacts without modifying the association of N-cadherin with catenins and its availability at the plasma membrane. Fluorescent recovery after photobleaching experiments demonstrate that at the dorsal plasma membrane, lipid rafts are not directly involved in the diffusional mobility of N-cadherin. In contrast, at cell-cell junctions N-cadherin association with lipid rafts allows its stabilization enabling the formation of a functional adhesive complex. We show that lipid rafts, as homophilic interaction and F-actin association, stabilize cadherin-dependent adhesive complexes. Homophilic interactions and F-actin association of N-cadherin are both required for its association to lipid rafts. We thus identify lipid rafts as new regulators of cadherin-mediated cell adhesion.