The sphingosine 1-phosphate receptor 5 and sphingosine kinases 1 and 2 are localised in centrosomes: Possible role in regulating cell division
The sphingosine 1-phosphate receptor 5 and sphingosine kinases 1 and 2 are localised in centrosomes: Possible role in regulating cell division
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DOI：
10.1016/j.cellsig.2009.01.023
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发表时间：
2009-05-01
影响因子：
4.8
通讯作者：
Pyne, Susan
中科院分区：
文献类型：
--
作者：
Gillies, Laura;Lee, Sue Chin;Pyne, Susan
我们在这里表明，内源性鞘氨醇1-磷酸5受体（S1 P（5），一种G蛋白偶联受体（GPCR），其天然配体是鞘氨醇1-磷酸（S1 P））和鞘氨醇激酶1和2（SK 1和SK 2），催化SIP的形成，共定位于哺乳动物细胞的中心体，在那里它们可能参与调节有丝分裂。中心体是涉及G蛋白、G（i）和微管蛋白的活性GTP-GDP循环的位点，它们是细胞分裂期间纺锤体极组织和力产生所需的。因此，S1 P（5）（其通常作为质膜鸟嘌呤核苷酸交换因子，GEF）和鞘氨醇激酶在中心体中的存在可能表明S1 P（5）可能作为配体激活的GEF在调节G蛋白依赖的纺锤体形成和有丝分裂中起作用。向细胞中加入SIP抑制了S1 P（5）向中心体的运输，表明了由细胞表面受体的配体占据控制的动态穿梭内吞机制。因此，我们认为中心体S1 P（5）受体可能是SIP的细胞内靶点，与有丝分裂的调节有关。(C)2009 Elsevier Inc. All rights reserved.
We show here that the endogenous sphingosine 1-phosphate 5 receptor (S1P(5), a G protein coupled receptor (GPCR) whose natural ligand is sphingosine 1-phosphate (S1P)) and sphingosine kinases 1 and 2 (SK1 and SK2), which catalyse formation of SIP, are co-localised in the centrosome of mammalian cells, where they may participate in regulating mitosis. The centrosome is a site for active GTP-GDP cycling involving the G-protein, G(i) and tubulin, which are required for spindle pole organization and force generation during cell division. Therefore, the presence of S1P(5) (which normally functions as a plasma membrane guanine nucleotide exchange factor, GEF) and sphingosine kinases in the centrosome might suggest that S1P(5) may function as a ligand activated GEF in regulating G-protein-dependent spindle formation and mitosis. The addition of SIP to cells inhibits trafficking of S1P(5) to the centrosome, suggesting a dynamic shuttling endocytic mechanism controlled by ligand occupancy of cell surface receptor. We therefore propose that the centrosomal S1P(5) receptor might function as an intracellular target of SIP linked to regulation of mitosis. (C) 2009 Elsevier Inc. All rights reserved.