Nectin-3, a new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities
Nectin-3, a new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities
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DOI：
10.1074/jbc.275.14.10291
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发表时间：
2000-04-07
影响因子：
4.8
通讯作者：
Takai, Y
中科院分区：
文献类型：
--
作者：
Satoh-Horikawa, K;Nakanishi, H;Takai, Y
我们分离到一个位于钙粘蛋白粘附连接处的新的细胞-细胞粘附系统，该系统至少由非Ca ~（2+）依赖性免疫球蛋白样粘附分子nectin和连接nectin与肌动蛋白细胞骨架的afadin组成，Nectin构成由nectin-1和nectin-2两个成员组成的家族，我们在这里分离了连接蛋白家族的第三个成员，并将其命名为连接蛋白-3，连接蛋白-3有三种剪接变体，连接蛋白-3 α（最大），-3 β（中间）和-3 γ（最小）。与nectin-1和nectin-2一样，nectin-3 α由三个细胞外免疫球蛋白样结构域、一个跨膜片段和一个具有C-末端共有基序的细胞质区域组成，用于结合PDZ结构域。Nectin-3 α形成顺式同源二聚体，并显示Ca 2+非依赖性反式同源相互作用，以引起血友病细胞-细胞粘附。此外，Nectin-3 α显示与Nectin-1或-2的反式异源相互作用，但不与Nectin-1或-2形成顺式异源二聚体，Nectin-1不显示与Nectin-2的反式异源相互作用。nectin-3 α与nectin-1或-2的反式异源相互作用的亲和力高于nectin-1、-2或-3 α的反式同源相互作用的亲和力。Nectin-2和Nectin-3广泛表达，而Nectin-1在脑中大量表达。Nectin-3 α与Nectin-2共定位在基于钙粘蛋白的AJs上，并与afadin相互作用。这些结果表明，Nectin家族至少由三个成员组成，Nectin-1，-2和-3，所有这些成员都显示嗜血和嗜异性细胞-细胞粘附活性，并定位在基于钙粘蛋白的AJs上。
We have isolated a novel cell-cell adhesion system localized at cadherin-based adherens junctions (AJs), This system consists of at least nectin, a Ca2+ -independent immunoglobulin-like adhesion molecule, and afadin, an actin filament-binding protein, that connects nectin to the actin cytoskeleton, Nectin constitutes a family consisting of two members, nectin-1 and -2, We have isolated here a third member of the nectin family and named it nectin-3, Nectin-3 has three splicing variants, nectin-3 alpha (biggest), -3 beta (middle), and -3 gamma (smallest). Like nectin-1 and -2, nectin-3 alpha consists of three extracellular immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic region with the C-terminal consensus motif for binding to the PDZ domain. Nectin-3 alpha formed a cis-homo-dimer and showed Ca2+ -independent trans-homo-interaction to cause hemophilic cell-cell adhesion. Nectin-3 alpha furthermore showed trans-hetero-interaction with nectin-1 or -2 but did not form a cis-hetero-dimer with nectin-1 or -2, Nectin-1 did not show trans-heterointeraction with nectin-2. The affinity of trans-heterointeraction of nectin-3 alpha with nectin-1 or -2 was higher than that of trans homo-interaction of nectin-1, -2, or -3 alpha. Nectin-2 and -3 were ubiquitously expressed, whereas nectin-1 was abundantly expressed in brain. Nectin-3 alpha was colocalized with nectin-2 at cadherin-based AJs and interacted with afadin, These results indicate that the nectin family consists of at least three members, nectin-1, -2, and -3, all of which show hemophilic and heterophilic cell-cell adhesion activities and are localized at cadherin-based AJs.