Rathjen Fritz G
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Bioessays. 2020 Dec;42(12):e2000031. doi: 10.1002/bies.202000031. Epub 2020 Nov 10.
Members of the CAR group of Ig-like type I transmembrane proteins mediate homotypic cell adhesion, share a common overall extracellular domain structure and are closely related at the amino acid sequence level. CAR proteins are often found at tight junctions and interact with intracellular scaffolding proteins, suggesting that they might modulate tight junction assembly or function. However, impairment of tight junction integrity has not been reported in mouse knockout models or zebrafish mutants of CAR members. In contrast, in the same knockout models deficits in gap junction communication were detected in several organ systems, including the atrioventricular node of the heart, smooth muscle cells of the intestine and the ureter and in Sertoli cells of the testes. Possible interactions between BT-IgSF and connexin41.8 on the disturbed pattern of pigment stripes found in zebrafish mutants and between ESAM and connexin43 during hematopoiesis in the mouse are also discussed. On the basis of the combined data and phenotypic similarities between CAR member mutants and connexin mutants I hypothesize that they primarily play a role in the organization of gap junction communication. Also see the video abstract here: https://youtu.be/i0yq2KhuDAE.
免疫球蛋白样I型跨膜蛋白CAR家族成员介导同型细胞黏附，具有共同的整体细胞外结构域结构，且在氨基酸序列水平上密切相关。CAR蛋白常存在于紧密连接处，并与细胞内支架蛋白相互作用，这表明它们可能调节紧密连接的组装或功能。然而，在CAR家族成员的小鼠基因敲除模型或斑马鱼突变体中，尚未报道紧密连接完整性受损的情况。相反，在相同的基因敲除模型中，在包括心脏房室结、肠道平滑肌细胞、输尿管以及睾丸支持细胞在内的多个器官系统中，检测到缝隙连接通讯存在缺陷。还讨论了斑马鱼突变体中色素条纹紊乱模式下BT-IgSF与连接蛋白41.8之间以及小鼠造血过程中ESAM与连接蛋白43之间可能的相互作用。基于CAR家族成员突变体与连接蛋白突变体之间的综合数据和表型相似性，我推测它们主要在缝隙连接通讯的组织中发挥作用。另请在此处查看视频摘要：https://youtu.be/i0yq2KhuDAE。
