Localization and function of Arf family GTPases
Localization and function of Arf family GTPases
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DOI：
10.1042/bst0330639
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发表时间：
2005-08-01
影响因子：
3.9
通讯作者：
Honda, A
中科院分区：
文献类型：
--
作者：
Donaldson, JG;Honda, A
Arfs是Ras相关的GTP结合蛋白家族，其在调节膜运输和结构中起作用。六种哺乳动物Arf蛋白普遍表达，因此预期每种蛋白在细胞内具有不同的定位和功能。已经假定，这种特异性的大部分将通过确定Arf的哪些调节剂、GEF（鸟嘌呤核苷酸交换因子）和GAPS（GTP酶激活蛋白）与哪些Arf蛋白一起起作用来确定。尽管体外测定可以指示对于已经鉴定的许多Arf GEF和GAPS的Arf偏好，但是在细胞中，不同的Arf、GEF和GAPS靶向于它们执行其功能的特定隔室。我们已经开始研究，以确定区域的Arf 1和Arf 6蛋白，决定其网站的行动和具体活动分别在高尔基体和质膜。在Arf 1和Arf 6之间制造嵌合体，以鉴定有助于靶向和功能的蛋白质区域。然而Arf 6通过沿着蛋白质的多个区域沿着靶向质膜，我们已经在Arf 1中发现了足以将Arf 6靶向Goigi复合物的Golgi靶向区域。
Arfs are a family of Ras-related GTP-binding proteins that function in the regulation of membrane trafficking and structure. The six mammalian Arf proteins are expressed ubiquitously and so it is anticipated that each will have a distinct localization and function within the cell. it has been assumed that much of this specificity will be defined by determining which regulators of Arfs, the GEFs (guanine nucleotide-exchange factors) and GAPS (GTPase-activating proteins) function with which Arf proteins. Although in vitro assays may indicate Arf preferences for the numerous Arf GEFs and GAPS that have been identified, in the cell the different Arfs, GEFs and GAPS are targeted to specific compartments where they carry out their functions. We have embarked on studies to define regions of the Arf1 and Arf6 proteins that determine their sites of action and specific activities at the Golgi and plasma membrane respectively. Chimaeras were made between Arf1 and Arf6 in order to identify regions of the protein that contributed to targeting and function. Whereas Arf6 is targeted to the plasma membrane through multiple regions along the protein, we have found a Golgi-targeting region in Arf1 that is sufficient to target Arf6 to the Goigi complex.