Nectin : An Adhesion Molecule Involved in Formation-of Synaps

Nectin：一种参与突触形成的粘附分子

• 批准号: 12670014
• 负责人: MIZOGUCHI Akira
• 金额: $ 2.18万
• 依托单位: Mie University (2001)Kyoto University (2000)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670014/
• 关键词: Nectin; afadin; cadherin; puncta adherentia junctions; synaptic junctions; シナプス; 可塑性; Puncta Adherentia Junction; アドヘレンスジャンクション; タイトジャンクション

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.

Nectin-Afadin系统是一种新型的细胞 - 细胞粘附系统，该系统与上皮细胞中的钙粘蛋白 - 钙蛋白系统合作组织粘附联系。蜜饯是一种免疫球蛋白样粘附分子，Afadin是一种肌动蛋白丝结合蛋白，可连接蜜饯与肌动蛋白细胞骨架。纽约蛋白具有四个同工型（-1，-2，-3和-4）。每种蜜素形成一个均可分裂剂，然后形成均型二聚体，但nectin-3则形成带有Nectin-1或-2的异质反式二聚体，每个异质反式二聚体的形成比每种Homo-Trans-Trans-Trans-Dimer均具有强度。我们在这里表明，在成年小鼠海马体CA3区域的苔藓纤维末端和锥体细胞的树突之间的突触中，nectin- afadin系统与钙粘蛋白 - 催化蛋白系统以及Nectin-1和-3 nectin-1和-3 symetrentical synennipion in cyction in Cyction in Cyctication in Cycticaliaction syctaimiaction syctaimiaction inctaimiaction inctiaction syctaimiaction syctaciaction，nectin-1和-3无度地位。在开发过程中，Nectin -1和-3不对称地将不仅定位在圆顶座连接处，而且位于突触连接处。在培养的大鼠海马神经元中抑制nectin-1抑制剂基于粘液素的粘附会导致大小的降低和突触数量的增加。这些结果表明，蜜蜂 - 阿法丁系统在突触形成中的关键作用。

项目成果

Oh J, Takahashi R, Kondo S, Mizoguchi A, Adachi E, Sasahara RM, Nishimura S, Imamura Y, Kitayama H, Alexander DB, Ide C, Horan TP, Arakawa T., Yoshida H, Nishikawa S, Itoh Y, Seiki M, Itohara S, Takahashi C, Noda M.: "The membrane-anchored MMP inhibitor R

Oh J、高桥 R、近藤 S、沟口 A、足立 E、笹原 RM、西村 S、今村 Y、北山 H、亚历山大 DB、井出 C、霍兰 TP、荒川 T.、吉田 H、西川 S、伊藤 Y、精木

Mizoguchi A, Eguchi N, Kimura K, Kiyohara Y, Qu WM, Huang ZL, Mochizuki T, Lazarus M, Kobayashi T, Kaneko T, Narumiya S, Urade Y, Hayaishi O.: "Dominant localization of prostaglandin D receptor's on arachnoid trabecular cells in mouse basal forebrain and

Mizoguchi A、Eguchi N、Kimura K、Kiyohara Y、Qu WM、Huang ZL、Mochizuki T、Lazarus M、Kobayashi T、Kaneko T、Narumiya S、Urade Y、Hayaishi O.：“前列腺素 D 受体在蛛网膜小梁上的显性定位

Tanaka M, Miyoshi J, Ishizaki H, Togawa A, Ohnishi K, Endo K, Matsubara K, Mizoguchi A, Nagano T, Sato M, Sasaki T, Takai Y.: "Role of rab3 gdp/gtp exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction"Mol Biol Cell. 12(5).

Tanaka M、Miyoshi J、Ishizaki H、Tokawa A、Ohnishi K、Endo K、Matsubara K、Mizoguchi A、Nagano T、Sato M、Sasaki T、Takai Y.：“rab3 gdp/gtp 交换蛋白在突触小泡运输中的作用

Shirusu,H,Kimara,K.,Mizoguchi,A., et al: "VAMP-Z promotes neurite eleongetion and SNAP-25A increases nearite spreating in PCIZ cells"Nearoscience Research. 37. 265-275 (2000)

Shirusu,H,Kimara,K.,Mizoguchi,A.等人：“VAMP-Z 促进 PCIZ 细胞中的神经突伸长，SNAP-25A 增加近端扩散”Nearoscience Research。

Nishida A, Takahashi M, Tanihara H, Nakano I, Takahashi J, Mizoguchi A, Ide C, Honda Y.: "Incorporation and differentiation of hippocampus-derived neuronal stem cells transplanted in injured adult rat retina"Invest Ophthalmol Vis Sci. 41. 4268-4274 (2000)

Nishida A、Takahashi M、Tanihara H、Nakano I、Takahashi J、Mizoguchi A、Ide C、Honda Y.：“移植到受伤成年大鼠视网膜中的海马源性神经干细胞的掺入和分化”Invest Ophasemol Vis Sci。