RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin.
RINL, guanine nucleotide exchange factor Rab5-subfamily, is involved in the EphA8-degradation pathway with odin.
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DOI：
10.1371/journal.pone.0030575
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Katada T
中科院分区：
文献类型：
--
作者：
Kajiho H;Fukushima S;Kontani K;Katada T
小的鸟苷三磷酸酶（GTP酶）的Rab家族在膜运输中起着至关重要的作用。其活性GTP结合状态由鸟嘌呤核苷酸交换因子（GEF）驱动。Ras和Rab相互作用（或Ras相互作用/干扰）样蛋白（RINL）是一个新的Rab 5亚家族GEF，它含有一个保守的VPS 9结构域，对GEF的作用至关重要。然而，其详细的功能和相互作用的分子尚未完全阐明。在这里，我们发现RINL具有GEF活性的Rab 5亚家族蛋白，通过测量其在培养细胞中的GTP结合形式。我们还发现，RINL与odin相互作用，odin是含锚重复和不育α基序（SAM）结构域（Anks）蛋白家族的成员。此外，Eph酪氨酸激酶受体EphA 8与RINL和odin形成三元复合物。有趣的是，培养细胞中的RINL表达以依赖于其GEF活性和与odin相互作用的方式降低EphA 8水平。此外，RINL的敲低增加了HeLa细胞中的EphA 8水平。我们的研究结果表明，RINL作为Rab 5亚家族的GEF，通过与odin的相互作用参与EphA 8降解途径。
The Rab family of small guanosine triphosphatases (GTPases) plays a vital role in membrane trafficking. Its active GTP-bound state is driven by guanine nucleotide-exchange factors (GEFs). Ras and Rab interactor (or Ras interaction/interference)-like (RINL), which contains a conserved VPS9 domain critical for GEF action, was recently identified as a new Rab5 subfamily GEF in vitro. However, its detailed function and interacting molecules have not yet been fully elucidated. Here we found that RINL has GEF activity for the Rab5 subfamily proteins by measuring their GTP-bound forms in cultured cells. We also found that RINL interacts with odin, a member of the ankyrin-repeat and sterile-alpha motif (SAM) domain-containing (Anks) protein family. In addition, the Eph tyrosine kinase receptor EphA8 formed a ternary complex with both RINL and odin. Interestingly, RINL expression in cultured cells reduced EphA8 levels in a manner dependent on both its GEF activity and interaction with odin. In addition, knockdown of RINL increased EphA8 level in HeLa cells. Our findings suggest that RINL, as a GEF for Rab5 subfamily, is implicated in the EphA8-degradation pathway via its interaction with odin.
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