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.

connectin -afadin系统是上皮细胞中与cadherin-catenin系统协同组织粘附连接的一种新型细胞-细胞粘附系统。连接蛋白是一种类似免疫球蛋白的粘附分子，而黄豆素是一种连接连接蛋白和肌动蛋白细胞骨架的肌动蛋白丝结合蛋白。连接蛋白有四种异构体（-1、-2、-3和-4）。每一种连接素先形成同型顺式二聚体，再形成同型反式二聚体，而连接素-3又与连接素-1或-2形成异型反式二聚体，且各异型反式二聚体的形成强于各同型反式二聚体。我们发现，在成年小鼠海马CA3区苔藓纤维末端和锥体细胞树突之间的突触中，连接蛋白-afadin系统与钙粘蛋白-连环蛋白系统共定位，连接蛋白-1和-3分别不对称地定位于附着点连接的突触前和突触后侧。在发育过程中，连接蛋白-1和-3不仅不对称地定位于附着点连接处，也不对称地定位于突触连接处。在培养的大鼠海马神经元中，用连接素-1抑制剂抑制连接素为基础的粘附可导致突触大小的减小和突触数量的增加。这些结果表明连接素-afadin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

Tanaka M, Miyoshi J, Ishizaki H, Mizoguchi A, el.: "Role of rab3 gdp/gtp exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction"Mol Biol Cell. 12(5). 1421-1430 (2001)

Tanaka M、Miyoshi J、Ishizaki H、Mizoguchi A 等：“rab3 gdp/gtp 交换蛋白在小鼠神经肌肉接头突触小泡运输中的作用”Mol Biol Cell。

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。