Presynaptic regulation via mammalian homologues of Class C VPS

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SNARE分子相互作用，如syntaxin-1和nSec-1/Munc 18。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。

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.