Takatsu H, Yoshino K, Nakayama K
Institute of Biological Sciences, Gene Experiment Center, University of Tsukuba, Tsukuba Science City, Ibaraki, 305-8572, Japan.
Biochem Biophys Res Commun. 2000 May 19;271(3):719-25. doi: 10.1006/bbrc.2000.2700.
We identified a novel family of proteins that have a VHS domain and an AGEH (adaptor gamma ear homology) domain that is homologous to the ear domain of the gamma-adaptin subunit of the AP-1 clathrin adaptor. When overexpressed, the proteins, called GGA1, GGA2, and GGA3, localized to the trans-Golgi network (TGN) and often caused fragmentation and vacuolation of the compartment. Yeast two-hybrid analysis showed that the AGEH domains of the GGA proteins as well as those of gamma-adaptins are able to interact with gamma-synergin, which was previously shown to localized in the TGN region and interact with gamma-adaptin. Furthermore, gamma-synergin and either of the GGA proteins coexpressed were colocalized in the TGN region. These results suggest that the GGA proteins regulate the function of the TGN or membrane trafficking from this compartment and that the AGEH domains of GGAs and gamma-adaptins, like the ear domain of alpha-adaptin, are involved in interaction with molecules that modulate their functions.
我们鉴定出了一个新的蛋白质家族,它们具有VHS结构域和AGEH(衔接蛋白γ耳同源)结构域,该结构域与AP-1网格蛋白衔接蛋白的γ衔接蛋白亚基的耳结构域同源。当这些名为GGA1、GGA2和GGA3的蛋白质过表达时,它们定位于反式高尔基体网络(TGN),并常常导致该区室的碎片化和空泡化。酵母双杂交分析表明,GGA蛋白的AGEH结构域以及γ衔接蛋白的AGEH结构域能够与γ协同蛋白相互作用,γ协同蛋白先前已被证明定位于TGN区域并与γ衔接蛋白相互作用。此外,共表达的γ协同蛋白与任一GGA蛋白在TGN区域共定位。这些结果表明,GGA蛋白调节TGN的功能或从此区室进行的膜运输,并且GGA蛋白和γ衔接蛋白的AGEH结构域,如同α衔接蛋白的耳结构域一样,参与与调节其功能的分子的相互作用。