Halachmi N, Lev Z
Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
J Neurochem. 1996 Mar;66(3):889-97. doi: 10.1046/j.1471-4159.1996.66030889.x.
The Sec1 family, a novel family of proteins involved in synaptic transmission and general secretion, is described. To date, 14 members of this family have been identified: four yeast proteins, Sec1, Sly1, Slp1/Vps33, and Vps45/Stt10; three nematode proteins, Unc-18 and the homologues of Sly1 and Slp1; the Drosophila Rop; and six mammalian proteins, the rat Munc-18/n-Sec1/rbSec1A and rbSec1B, the mouse Munc-18b/muSec1 and Munc-18c, and the bovine Munc-18 and mSec1. The mammalian proteins share 44-63% sequence identity with the nematode Unc-18 and Drosophila Rop proteins and 20-29% with the yeast proteins and their nematode homologues. The Sec1 proteins are mostly hydrophilic and lack a transmembrane domain. Nevertheless, Sec1 proteins are found as membrane-bound proteins. Some of them are also found as soluble, cytoplasmic proteins. Binding of the rat brain Sec1 to the presynaptic membrane may be due to strong interaction with syntaxin, an integral component of this membrane. The rat brain Sec1 is also bound to Cdk5, a neural cyclin-dependent kinase. The Sec1 proteins play a positive role in exocytosis. Loss of function mutations in SEC1, SLY1, or SLP1 result in blocking of protein transport between distinct yeast sub-cellular compartments. Inactivation of unc-18 and rop results in inhibition of neurotransmitter release and, in the case of rop, inhibition of general secretion as well. In addition, studies of Rop and n-Sec1 indicate that they also play a negative role in synaptic transmission, mediated by their interaction with syntaxin. A working model addressing the dual regulative role of the Sec1 proteins in secretion is presented.
本文描述了Sec1家族，这是一个参与突触传递和一般分泌的新型蛋白质家族。迄今为止，已鉴定出该家族的14个成员：4种酵母蛋白，即Sec1、Sly1、Slp1/Vps33和Vps45/Stt10；3种线虫蛋白，即Unc-18以及Sly1和Slp1的同源物；果蝇的Rop；还有6种哺乳动物蛋白，即大鼠的Munc-18/n-Sec1/rbSec1A和rbSec1B、小鼠的Munc-18b/muSec1和Munc-18c，以及牛的Munc-18和mSec1。哺乳动物蛋白与线虫Unc-18和果蝇Rop蛋白的序列同一性为44%-63%，与酵母蛋白及其线虫同源物的序列同一性为20%-29%。Sec1蛋白大多具有亲水性，且缺乏跨膜结构域。然而，Sec1蛋白却以膜结合蛋白的形式存在。其中一些还以可溶性细胞质蛋白的形式存在。大鼠脑Sec1与突触前膜的结合可能是由于与Syntaxin（该膜的一个整合成分）的强烈相互作用。大鼠脑Sec1还与Cdk5（一种神经细胞周期蛋白依赖性激酶）结合。Sec1蛋白在胞吐作用中起积极作用。SEC1、SLY1或SLP1功能丧失突变会导致不同酵母亚细胞区室之间的蛋白质运输受阻。unc-18和rop失活会导致神经递质释放受到抑制，而就rop而言，还会抑制一般分泌。此外，对Rop和n-Sec1的研究表明，它们通过与Syntaxin相互作用，在突触传递中也起消极作用。本文提出了一个关于Sec1蛋白在分泌中双重调节作用的工作模型。
