UNC-108/Rab2 regulates postendocytic trafficking in Caenorhabditis elegans
UNC-108/Rab2 regulates postendocytic trafficking in Caenorhabditis elegans
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DOI：
10.1091/mbc.e07-11-1120
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发表时间：
2008-07-01
影响因子：
3.3
通讯作者：
Kaplan, Joshua M.
中科院分区：
文献类型：
--
作者：
Chun, Denise K.;McEwen, Jason M.;Kaplan, Joshua M.
在胞吞作用之后，膜蛋白通常在两种替代途径之间进行分类：再循环途径和降解途径。关于通过这些替代途径进行的贩运如何受到不同的监管，人们所知相对较少。在这里，我们确定了在神经元和体腔细胞中的胞内后运输的调节剂的β-108/Rab2。秀丽隐杆线虫Rab2基因unc-108的突变导致绿色荧光蛋白（GFP）标记的谷氨酸受体GLR-1（GLR-1：：GFP）在腹索和神经元细胞体中积累。在unc-108/Rab2突变体的神经元细胞体中，GLR-1：：GFP被发现在与早期和再循环内体的标记物（包括Syntaxin-13和Rab8）共定位的管状泡状结构中。GFP标记的Syntaxin-13也在unc-108/Rab2突变体的腹侧索中积累。泛素介导的GLR-1：：GFP分选进入多泡体（MVB）降解途径不需要GLR-108/Rab2。破坏MVB通路的突变和unc-108/Rab2突变对腹侧脊髓中的GLR-1：：GFP水平具有累加效应。在体腔细胞中，标记物德克萨斯红-牛血清白蛋白的胞后运输被延迟。这些结果表明，miR-108/Rab2调节内吞后运输，最有可能在早期或再循环内体的水平上，并且miR-108/Rab2和MVB途径定义了并行操作的替代内吞后运输机制。这些结果定义了Rab2在蛋白质运输中的新功能。
After endocytosis, membrane proteins are often sorted between two alternative pathways:a recycling pathway and a degradation pathway. Relatively little is known about how trafficking through these alternative pathways is differentially regulated. Here, we identify UNC-108/Rab2 as a regulator of postendocytic trafficking in both neurons and coelomocytes. Mutations in the Caenorhabditis elegans Rab2 gene unc-108, caused the green fluorescent protein (GFP)- tagged glutamate receptor GLR-1 (GLR-1::GFP) to accumulate in the ventral cord and in neuronal cell bodies. In neuronal cell bodies of unc-108/Rab2 mutants, GLR-1::GFP was found in tubulovesicular structures that colocalized with markers for early and recycling endosomes, including Syntaxin-13 and Rab8. GFP-tagged Syntaxin-13 also accumulated in the ventral cord of unc-108/Rab2 mutants. UNC-108/Rab2 was not required for ubiquitin-mediated sorting of GLR-1::GFP into the multivesicular body (MVB) degradation pathway. Mutations disrupting the MVB pathway and unc-108/Rab2 mutations had additive effects on GLR-1::GFP levels in the ventral cord. In coelomocytes, postendocytic trafficking of the marker Texas Red-bovine serum albumin was delayed. These results demonstrate that UNC-108/Rab2 regulates postendocytic trafficking, most likely at the level of early or recycling endosomes, and that UNC-108/Rab2 and the MVB pathway define alternative postendocytic trafficking mechanisms that operate in parallel. These results define a new function for Rab2 in protein trafficking.