Presynaptic regulation via mammalian homologues of Class C VPS

通过 C 类 VPS 的哺乳动物同源物进行突触前调节

• 批准号: 14580759
• 负责人: AKAZAWA Chihiro
• 金额: $ 2.3万
• 依托单位: National Center of Neurology and Psychiatry (NCNP)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580759/
• 关键词: RING-H2 domain; ubiguitin-proteasome; endosome-lysosome; synaptic transmission; syntaxin; yeast two hybrid; 神経細胞; 小胞輸送; エンドソーム; リソソーム; 細胞内局在; シナプス; 伝達物質放出; 酵母

Mammalian homologues of Class C VPS proteins play an essential role in the trafficking between endosome to lysosome. We investigated the potential role of Class C VPS proteins in rat brain. We found that Class C VPS proteins are predominantly expressed in neurons of whole brain regions. To investigate the molecular function, we searched the interacting molecules by using yeast two hybrid screening. Interestingly, Class C VPS proteins were shown to interact with presynaptic SNARE molecues, such as syntaxin-1 and nSec-1/Munc 18. In the HIT cells cotransfected with Class C VPS proteins and hGH reporter gene, the high concentration of KC1 (25mM) treatment induced the secretion of hGH and this increases were inhibited by Ca-channel blocker, nifedipine. These results suggest that Class C VPS proteins may be involved in Ca-dependent vesicle releases through interacting with neuronal SNARE, syntaxin-1 and nSec-1/Munc 18.

C类VPS蛋白的哺乳动物同源物在内体到溶酶体之间的运输中起重要作用。我们研究了C类VPS蛋白在大鼠脑中的潜在作用。我们发现C类VPS蛋白主要在整个脑区域的神经元中表达。为了研究其分子功能，我们利用酵母双杂交技术筛选相互作用的分子。有趣的是，C类VPS蛋白被证明与突触前陷阱分子（例如syntaxin-1和nSec-1/Munc 18）相互作用。在共转染C类VPS蛋白和hGH报告基因的HIT细胞中，高浓度的KCl（25 mM）处理诱导hGH的分泌，这种增加被钙通道阻断剂硝苯地平抑制。这些结果表明，C类VPS蛋白可能通过与神经元SNARE，syntaxin-1和nSec-1/Munc 18相互作用参与钙依赖性囊泡释放。

项目成果

Kim BY, Ueda M, Kominami E, Kohsaka S, Akazawa C: "Identification of mouse Vps16 and biochemical characterization of mammalian Class C Vps complex"BBRC. vol.311. 577-582 (2003)

Kim BY、Ueda M、Kominami E、Kohsaka S、Akazawa C：“小鼠 Vps16 的鉴定和哺乳动物 C 类 Vps 复合物的生化特征”BBRC。

Yo Sasaki et al.: "Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain"Glia. 44. 242-250 (2003)

Yo Sasaki 等人：“大鼠脑小胶质细胞中 Gi/o 偶联 ATP 受体 P2Y12 的选择性表达”

Kim BY, Ueda M, Nakamura Y, Kohsaka S, Akazawa C: "Expression of the mammalian homologue of vacuolar protein sorting (Vps16p) in the mouse and rat brain"Neuroscience Letters. vol.355. 217-220 (2004)

Kim BY、Ueda M、Nakamura Y、Kohsaka S、Akazawa C：“小鼠和大鼠大脑中液泡蛋白分选的哺乳动物同源物 (Vps16p) 的表达”《神经科学快报》。

Akazawa C, Nakamura Y, Sango K, Horie H, Kohsaka S: "Distribution of the galectin-1 mRNA in the rat nervous system ; its transient upregulation in rat facial motor neurons after facial nerve axotomy"Neuroscience. vol.125. 171-178 (2004)

Akazawa C、Nakamura Y、Sango K、Horie H、Kohsaka S：“大鼠神经系统中 galectin-1 mRNA 的分布；面神经轴索切除术后大鼠面部运动神经元的瞬时上调”神经科学。

Chihiro Akazawa et al.: "Distribution of the galectin-1 mRNA in the rat nervous system ; its transient upregulation in rat facial motor neurons after facial nerve axotomy"Neuroscience. 125. 171-178 (2004)

Chihiro Akazawa 等人：“大鼠神经系统中半乳糖凝集素-1 mRNA 的分布；面神经轴突切除术后大鼠面部运动神经元的瞬时上调”神经科学。