A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome.
A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome.
复制标题
DOI：
10.1083/jcb.149.1.67
复制
发表时间：
2000-04-03
影响因子：
7.8
通讯作者：
Robinson, M S
中科院分区：
文献类型：
--
作者：
Hirst, J;Lui, W W;Bright, N A;Totty, N;Seaman, M N;Robinson, M S
我们已经克隆并鉴定了一个新的蛋白质家族——GGAs的成员。这些蛋白质包含一个氨基末端的VHS结构域、一个或两个卷曲螺旋结构域，以及一个与γ-衔接蛋白的羧基末端“耳”结构域同源的羧基末端结构域。然而，与γ-衔接蛋白不同的是，GGAs不与网格蛋白包被的囊泡或AP - 1复合物的任何成分相关联。GGA1和GGA2彼此之间也不相关联，尽管它们共定位在核周膜上。免疫金电子显微镜显示这些膜对应于高尔基体堆叠的反面元件和反面高尔基网络（TGN）。谷胱甘肽S - 转移酶（GST）下拉实验表明，GGA的羧基末端结构域与一部分能结合γ-衔接蛋白羧基末端结构域的蛋白质相结合。在酵母中存在两个GGA基因。删除这两个基因会导致液泡酶羧肽酶Y的错误分选，并且细胞还具有液泡形态缺陷的表型。这些结果表明，GGAs的功能是促进蛋白质在反面高尔基网络（TGN）和液泡之间，或者在其哺乳动物等效物溶酶体之间的运输。
We have cloned and characterized members of a novel family of proteins, the GGAs. These proteins contain an NH2-terminal VHS domain, one or two coiled-coil domains, and a COOH-terminal domain homologous to the COOH-terminal “ear” domain of γ-adaptin. However, unlike γ-adaptin, the GGAs are not associated with clathrin-coated vesicles or with any of the components of the AP-1 complex. GGA1 and GGA2 are also not associated with each other, although they colocalize on perinuclear membranes. Immunogold EM shows that these membranes correspond to trans elements of the Golgi stack and the TGN. GST pulldown experiments indicate that the GGA COOH-terminal domains bind to a subset of the proteins that bind to the γ-adaptin COOH-terminal domain. In yeast there are two GGA genes. Deleting both of these genes results in missorting of the vacuolar enzyme carboxypeptidase Y, and the cells also have a defective vacuolar morphology phenotype. These results indicate that the function of the GGAs is to facilitate the trafficking of proteins between the TGN and the vacuole, or its mammalian equivalent, the lysosome.