Molecular mechanism of strengthening synaptic connection by neural activity.

通过神经活动加强突触连接的分子机制。

• 批准号: 13480261
• 负责人: YAMAGATA Kanato
• 金额: $ 9.66万
• 依托单位: Tokyo Metropolitan Institute for Neuroscience
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13480261/
• 关键词: neural activity; cell adhesion molecule; cadherin; 神経接着分子; MAP kinase

We investigated the role of activity-regulated adhesion molecule arcadlin. Arcadlin is synthesized in neurons and carried to synapses and may be involved in synaptic reorganization stimulated by synaptic activity. Here, we analyzed the interaction of TAO2 with the cytoplasmic region of Arcadlin. Homophilic binding of extracellular (EC) domains of arcadlin activated TAO2 and its down-stream kinases, MKK3 and p38 MAP kinase. The homophilic interaction also induced the internalization of arcadlin itself. This internalization was completely blocked by the co-expression of dominant-negative dynamin, indicating that arcadlin was internalized by clathrin-mediated endocytosis. The absence of MKK3 and p38 MARK resulted in a loss of arcadlin endocytosis. Moreover, p38 MARK inhibitor SB203580 also inhibited the endocytosis of arcadlin. These results suggest that TAO2, stimulated by homophilic binding of arcadlin EC domains, activates p38 MAP kinase pathway and induces the endocytosis of arcadlin. Thus, neural activity may play a role in changing the strength of synaptic connections by regulating the number of cell adhesion molecules on the surface of synaptic membranes.

我们研究了活性调节粘附分子arcadlin的作用。Arcadlin在神经元中合成并被运送到突触，并且可能参与由突触活动刺激的突触重组。在这里，我们分析了TAO2与Arcadlin胞质区域的相互作用。Arcadlin的细胞外（EC）结构域的嗜同性结合激活TAO 2及其下游激酶MKK 3和p38 MAP激酶。嗜同性相互作用也诱导了Arcadlin自身的内化。这种内化被显性负性发动蛋白的共表达完全阻断，表明arcadlin通过网格蛋白介导的内吞作用内化。MKK3和p38 MARK的缺失导致Arcadlin内吞作用的丧失。此外，p38 MARK抑制剂SB 203580也抑制了Arcadlin的内吞作用。这些结果表明，TAO 2，刺激嗜同性结合的arcadlin EC结构域，激活p38 MAP激酶途径，并诱导内吞的arcadlin。因此，神经活动可能通过调节突触膜表面的细胞粘附分子的数量而在改变突触连接的强度中发挥作用。

项目成果

Matsuoka M. et al.: "Expression and regulation of the immediate-early gene product Arc in the accessory olfactory bulb after mating in male rat"Neuroscience. 111(2). 251-258 (2002)

Matsuoka M. 等人：“雄性大鼠交配后副嗅球中立即早期基因产物 Arc 的表达和调节”神经科学。

Matsuoka M. et al.: "Expression and regulation of the immediate-early gene product Arc in the accessory olfactory bulb after mating in male rat"Neuroscience. (in press). (2002)

Matsuoka M. 等人：“雄性大鼠交配后副嗅球中立即早期基因产物 Arc 的表达和调节”神经科学。

Matsumura K. et al.: "COX-2 and mPGES in bain endothelial cells : potential targets of anti-inflammentory drugs"Current Medical Chemistry. 1. 161-166 (2002)

Matsumura K. 等人：“bain 内皮细胞中的 COX-2 和 mPGES：抗炎药物的潜在靶标”当前医学化学。

Matsuoka M, et al.: "Expression and regulation of the immediate-early gene product Arc in the accessory olfactory bulb after mating in male rat"Neuroscience. 111(2). 251-258 (2002)

Matsuoka M 等人：“雄性大鼠交配后副嗅球中立即早期基因产物 Arc 的表达和调节”神经科学。

Yamagata K, et al.: "Coexpression of microsomal-type prostaglandin E synthase with cyclooxygenase-2 in brain endotherial cells of rats during endotoxm-induced fever"J. Neurosci.. 21(8). 2669-2677 (2001)

Yamagata K, et al.：“内毒素引起发热期间大鼠脑内皮细胞中微粒体型前列腺素 E 合酶与环氧合酶 2 的共表达”J.