Acute perturbations in Golgi organization impact de novo sphingomyelin synthesis.

Acute perturbations in Golgi organization impact de novo sphingomyelin synthesis.
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DOI:
10.1111/j.1600-0854.2008.00810.x
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发表时间:
2008-11
期刊:
Traffic (Copenhagen, Denmark)
影响因子:
--
通讯作者:
Machamer CE
Machamer CE
中科院分区:
其他
文献类型:
--
作者:
Chandran S;Machamer CE

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哺乳动物的高尔基体是由多个堆叠的池膜横向组织成一个带状结构,与专门的内质网(ER)膜的transGolgi区域紧密并列。这些接触可能是神经酰胺通过神经酰胺转移蛋白(CERT)从其合成位点(ER)转移到鞘磷脂(SM)合酶的位点。CERT从ER中提取神经酰胺并将其转移到高尔基体膜,但整个高尔基体结构在此过程中的作用尚不清楚。我们在这里表明,本地化的CERT在斑点周围的高尔基复合体需要ER和高尔基结合域的CERT。为了研究高尔基体结构如何促进SM合成,我们用高尔基体干扰药物处理细胞并测量新合成的SM。有趣的是,诺考达唑破坏高尔基体形态,但不破坏伊马醌,会抑制SM合成。减少定位CERT与高尔基体标记与SM合成减少。我们建议,一些高尔基体结构扰动干扰有效的神经酰胺贩运通过CERT,从而SM合成。哺乳动物高尔基带的组织与CERT一起可以促进特定的ER-高尔基体相互作用,以有效地递送神经酰胺用于SM合成。
The mammalian Golgi apparatus is composed of multiple stacks of cisternal membranes organized laterally into a ribbon-like structure, with close apposition of trans Golgi regions with specialized endoplasmic reticulum (ER) membranes. These contacts may be the site of ceramide transfer from its site of synthesis (ER) to sphingomyelin (SM) synthase via ceramide transfer protein (CERT). CERT extracts ceramide from the ER and transfers it to Golgi membranes, but the role of overall Golgi structure in this process is unknown. We show here that localization of CERT in puncta around the Golgi complex requires both ER and Golgi binding domains of CERT. To examine how Golgi structure contributes to SM synthesis, we treated cells with Golgi perturbing drugs and measured newly synthesized SM. Interestingly, disruption of Golgi morphology with nocodazole, but not ilimaquinone inhibited SM synthesis. Decreased localization of CERT with a Golgi marker correlated with decreased SM synthesis. We propose that some Golgi structural perturbations interfere with efficient ceramide trafficking via CERT, and thus SM synthesis. The organization of the mammalian Golgi ribbon together with CERT may promote specific ER-Golgi interactions for efficient delivery of ceramide for SM synthesis.
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