Nectin : An Adhesion Molecule Involved in Formation-of Synaps

nectin-afadin系统是一种新型的细胞间粘附系统，它与上皮细胞中的钙粘蛋白-连环蛋白系统协同作用形成粘附连接。Nectin是一种免疫球蛋白样粘附分子，afadin是一种肌动蛋白亲和结合蛋白，将Nectin连接到肌动蛋白细胞骨架。Nectin有四种亚型（-1，-2，-3和-4）。每个nectin形成一个同-顺-二聚体，然后形成一个同-反-二聚体，但nectin-3还与nectin-1或-2形成一个异-反-二聚体，并且每个异-反-二聚体的形成比每个同-反-二聚体的形成更强。我们在这里表明，在苔藓纤维终端和树突之间的突触在成年小鼠海马CA 3区的锥体细胞，nectin-afadin系统colocalizes与钙粘蛋白-连环蛋白系统和nectin-1和-3不对称定位在突触前和突触后侧的斑点adherentia连接，分别。在发育过程中，nectin-1和nectin-3不仅不对称地定位于粘附点连接处，而且还定位于突触连接处。在培养的大鼠海马神经元中，通过nectin-1的抑制剂抑制基于nectin的粘附导致突触的大小减小和伴随的数目增加。这些结果表明nectin-afadin系统在突触形成中的关键作用。

The nectin-afadin system is a novel cell-cell adhesion system that organizes adherens junctions cooperatively with the cadherin-catenin system in epithelial cells. Nectin is an immunoglobulin-like adhesion molecule, and afadin is an actin filament-binding protein that connects nectin to the actin cytoskeleton. Nectin has four isoforms (-1, -2, -3, and -4). Each nectin forms a homo-cis-dimer followed by formation of a homo-trans-dimer, but nectin-3 furthermore forms a hetero-trans-dimer with nectin-1 or -2, and the formation of each hetero-trans-dimer is stronger than that of each homo-trans-dimer. We show here that at the synapses between the mossy fiber terminals and the dendrites of pyramidal cells in the CA3 area of adult mouse hippocampus, the nectin-afadin system colocalizes with the cadherin-catenin system and that nectin-1 and -3 asymmetrically localize at the presynaptic and postsynaptic sides of puncta adherentia junctions, respectively. During development, nectin-1 and -3 asymmetrically localize not only at puncta adherentia junctions but also at synaptic junctions. Inhibition of the nectin-based adhesion by an inhibitor of nectin-1 in cultured rat hippocampal neurons results in decrease in size and concomitant increase in number of synapses. These results indicate a key role of the nectin-afadin system in formation of synapses.