Evidence for secretory pathway localization of a voltage-dependent anion channel isoform.
Evidence for secretory pathway localization of a voltage-dependent anion channel isoform.
复制标题
DOI：
10.1073/pnas.97.7.3201
复制
发表时间：
2000-03
影响因子：
11.1
通讯作者：
Reinhard Buettner;Georg Papoutsoglou;Eliana Scemes;D. Spray;Rolf Dermietzel
中科院分区：
文献类型：
--
作者：
Reinhard Buettner;Georg Papoutsoglou;Eliana Scemes;D. Spray;Rolf Dermietzel
电压依赖性阴离子通道（VDACs）是一种成孔蛋白（孔蛋白），是腺嘌呤核苷酸通过线粒体外膜的主要通道。电生理学研究表明，VDAC样通道活性也普遍存在于许多哺乳动物细胞的细胞膜中。然而，线粒体外孔蛋白的多拓扑定位仍然是一个极具争议的问题。在此，我们表明，使用两个替代的第一外显子的小鼠VDAC-1基因导致两个孔蛋白的表达不同的N末端。一种含有疏水前导肽的孔蛋白（质膜VDAC-1）主要通过高尔基体靶向细胞膜。相反，缺乏N-末端前导序列的第二种亚型（线粒体VDAC-1）更有效地易位到线粒体外膜中。因此，我们的数据提供了独特的遗传证据，有利于线粒体孔蛋白的多拓扑定位。
Voltage-dependent anion channels (VDACs) are pore-forming proteins (porins) that form the major pathway for movement of adenine nucleotides through the outer mitochondrial membrane. Electrophysiological studies indicate that VDAC-like channel activity is also prevalent in the cell membranes of many mammalian cells. However, the multitopological localization of porins outside the mitochondrion has remained an extremely controversial issue. Herein, we show that usage of two alternative first exons of the murine VDAC-1 gene leads to expression of two porins differing within their N termini. One porin (plasmalemmal VDAC-1) harboring a hydrophobic leader peptide is primarily targeted through the Golgi apparatus to the cell membrane. In contrast, the second isoform lacking the N-terminal leader (mitochondrial VDAC-1) is translocated more efficiently into the outer mitochondrial membrane. Thus, our data provide unique genetic evidence in favor of a multitopological localization of a mitochondrial porin.