Cannabinoid receptor 2 undergoes Rab5-mediated internalization and recycles via a Rab11-dependent pathway
Cannabinoid receptor 2 undergoes Rab5-mediated internalization and recycles via a Rab11-dependent pathway
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DOI：
10.1016/j.bbamcr.2011.05.010
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发表时间：
2011-08-01
影响因子：
5.1
通讯作者：
Glass, Michelle
中科院分区：
文献类型：
--
作者：
Grimsey, Natasha L.;Goodfellow, Catherine E.;Glass, Michelle
大麻素受体2 （Cannabinoid receptor 2, CB2）是一种在免疫系统细胞表面高度表达的GPCR，支持其在免疫调节中的作用。本研究考察了该受体在HEK-293细胞稳定表达时的转运特性。正如先前报道的那样，暴露于激动剂后，细胞表面CB2迅速内化。CB2循环的直接证据是在刺激激动剂被反向激动剂竞争性去除时观察到的。在没有激动剂的情况下，CB2也经历了缓慢的本构内化，在有逆激动剂的情况下，CB2上调。CB2和显性阴性Rab5的共表达导致受体内化能力显著降低，但对内化受体的再循环没有影响。相反，与显性阴性Rab11共表达不会改变CB2内化的能力，但会损害CB2返回细胞表面的能力。野生型、显性阴性或组成活性Rab4与CB2的共表达不会改变基底表面表达、内化程度或再循环程度。这些结果表明Rab5参与了CB2的内吞作用，并且内化受体通过Rab11相关途径而不是Rab4相关途径进行循环。该报告提供了迄今为止CB2内部化和回收的第一个全面描述。(C) 2011 Elsevier B.V.版权所有
Cannabinoid receptor 2 (CB2) is a GPCR highly expressed on the surface of cells of the immune system, supporting its role in immunomodulation. This study has investigated the trafficking properties of this receptor when stably expressed by HEK-293 cells. As previously reported, cell surface CB2 rapidly internalized upon exposure to agonist. Direct evidence of CB2 recycling was observed upon competitive removal of the stimulating agonist by inverse agonist. CB2 also underwent slow constitutive internalization when agonist was absent and was up-regulated in the presence of inverse agonist. Co-expression of CB2 and dominant negative Rab5 resulted in a significantly reduced capacity for receptors to internalize with no effect on recycling of the internalized receptors. Conversely, co-expression with dominant negative Rab11 did not alter the ability of CB2 to internalize but did impair their ability to return to the cell surface. Co-expression of wildtype, dominant negative or constitutively active Rab4 with CB2 did not alter basal surface expression, extent of internalization, or extent of recycling. These results suggest that Rab5 is involved in CB2 endocytosis and that internalized receptors are recycled via a Rab11 associated pathway rather than the rapid Rab4 associated pathway. This report provides the first comprehensive description of CB2 internalization and recycling to date. (C) 2011 Elsevier B.V. All rights reserved.