Institute-associated Research Group "Cell adhesion and cell polarity", ZMBE, University of Münster, D-48149 Münster, Germany.
Institute of Medical Biochemistry, ZMBE, University of Münster, D-48149 Münster, Germany.
Sci Signal. 2022 Sep 13;15(751):eabm2449. doi: 10.1126/scisignal.abm2449.
Intestinal epithelial cells absorb nutrients through the brush border, composed of dense arrays of highly ordered microvilli at their apical membranes. A protocadherin-based intermicrovillar adhesion complex localized at microvilli tips mediates microvilli packing and organization. Here, we identified a second adhesion complex localized at the proximal base region of microvilli. This complex contained the immunoglobulin superfamily member TMIGD1, which directly interacted with the microvillar scaffolding proteins EBP50 and E3KARP. Complex formation with EBP50 required the activation of EBP50 by the actin-binding protein ezrin and was enhanced by the dephosphorylation of Ser in the PDZ2 domain of EBP50 by the phosphatase PP1α. Binding of the EBP50-ezrin complex to TMIGD1 enhanced the dynamic turnover of EBP50 at microvilli. Enterocyte-specific inactivation of in mice resulted in microvillar blebbing, loss of intermicrovillar adhesion, and perturbed brush border formation. Thus, we identified a second adhesion complex in microvilli and propose a mechanism that promotes microvillar formation and dynamics.
肠上皮细胞通过刷状缘吸收营养物质，刷状缘由其顶膜上密集排列的高度有序的微绒毛组成。定位于微绒毛尖端的原钙黏蛋白为基础的细胞间微绒毛黏附复合物介导微绒毛的包装和组织。在这里，我们鉴定了定位于微绒毛近端基部的第二个黏附复合物。该复合物包含免疫球蛋白超家族成员 TMIGD1，它直接与微绒毛支架蛋白 EBP50 和 E3KARP 相互作用。EBP50 与 TMIGD1 的复合物形成需要 EBP50 被肌动蛋白结合蛋白 ezrin 激活，并且由磷酸酶 PP1α 去磷酸化 EBP50 的 PDZ2 结构域中的 Ser 增强。EBP50-ezrin 复合物与 TMIGD1 的结合增强了 EBP50 在微绒毛上的动态周转。在小鼠中肠上皮细胞特异性敲除 导致微绒毛泡状化、细胞间微绒毛黏附丧失和刷状缘形成紊乱。因此，我们在微绒毛中鉴定了第二个黏附复合物，并提出了一种促进微绒毛形成和动力学的机制。
