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在麦迪逊-达比犬肾细胞中表达的促性腺激素和促甲状腺激素受体的基底外侧定位及转胞吞作用

Basolateral localization and transcytosis of gonadotropin and thyrotropin receptors expressed in Madin-Darby canine kidney cells.

作者信息

Beau I, Misrahi M, Gross B, Vannier B, Loosfelt H, Hai M T, Pichon C, Milgrom E

机构信息

Unité de Recherches Hormones et Reproduction, INSERM, Unité 135, Hôpital de Bicêtre, 94275 Le Kremlin Bicêtre, France.

出版信息

J Biol Chem. 1997 Feb 21;272(8):5241-8. doi: 10.1074/jbc.272.8.5241.

Abstract

The thyrotropin (TSH) and follicle-stimulating hormone (FSH) receptors are present mainly on the basolateral cell surface in the thyroid gland and in Sertoli cells, whereas in ovarian and in testicular cells, the luteinizing hormone (LH) receptors are distributed throughout the cell surface. When expressed in Madin-Darby canine kidney (MDCK) cells, all three receptors accumulated at the basolateral cell surface showing that they carry the corresponding targeting signals. The receptors were directly delivered to the basolateral surface of the MDCK cells. A minor fraction of the gonadotropin receptors but not of TSH receptors was secondarily targeted to the apical surface through transcytosis. The mechanisms of basolateral targeting and transcytosis were analyzed using the FSH receptor as a model. Both were insensitive to brefeldin A and pertussis toxin. Gs activation by AlF4- and cholera toxin provoked a marked enhancement of FSH receptor transcytosis. The population of Gs proteins involved in this mechanism was different from that involved in signal transduction since neither FSH nor forskolin mimicked the effects of AlF4- and cholera toxin. Gs activation provoked a similar effect on LH receptor distribution in MDCK cells, whereas it did not modify the compartmentalization of the TSH receptor. Hormone-specific transcytosis was observed in MDCK cells expressing the gonadotropin (FSH and LH) receptors and was increased after cholera toxin administration.

摘要

促甲状腺激素(TSH)受体和促卵泡激素(FSH)受体主要存在于甲状腺和支持细胞的基底外侧细胞表面,而在卵巢细胞和睾丸细胞中,促黄体生成素(LH)受体则分布于整个细胞表面。当在犬肾传代细胞(MDCK)中表达时,所有这三种受体都在基底外侧细胞表面聚集,表明它们携带相应的靶向信号。这些受体直接被递送至MDCK细胞的基底外侧表面。一小部分促性腺激素受体(而非TSH受体)通过转胞吞作用被二次靶向至顶端表面。以FSH受体为模型分析了基底外侧靶向和转胞吞作用的机制。两者均对布雷菲德菌素A和百日咳毒素不敏感。AlF4-和霍乱毒素激活Gs会显著增强FSH受体的转胞吞作用。参与该机制的Gs蛋白群体与参与信号转导的不同,因为FSH和福斯高林均无法模拟AlF4-和霍乱毒素的作用。Gs激活对MDCK细胞中LH受体的分布产生类似影响,而对TSH受体的区室化没有影响。在表达促性腺激素(FSH和LH)受体的MDCK细胞中观察到了激素特异性转胞吞作用,并且在给予霍乱毒素后有所增加。

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