Newly characterized Golgi- localized family of proteins is involved in calcium and pH homeostasis in yeast and human cells
Newly characterized Golgi- localized family of proteins is involved in calcium and pH homeostasis in yeast and human cells
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DOI：
10.1073/pnas.1219871110
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发表时间：
2013-04-23
影响因子：
11.1
通讯作者：
Morsomme, Pierre
中科院分区：
文献类型：
--
作者：
Demaegd, Didier;Foulquier, Francois;Morsomme, Pierre
已知人类蛋白质TMEM 165的缺陷会导致先天性糖基化障碍的亚型。跨膜蛋白165（TMEM 165）属于未表征的膜蛋白家族，称为未表征的蛋白家族0016，其在整个进化过程中非常保守，并具有使人联想到阳离子/Ca 2+交换剂超家族的特征。Gcr 1依赖性翻译因子1（Gdt 1 p）是该家族的芽殖酵母成员，通过位于高尔基体中的未表征的Ca 2+转运途径促进Ca 2+稳态。发现gdt 1 Delta突变体对高浓度的Ca 2+敏感，有趣的是，这种敏感性被Gdt 1 p的人类直系同源物TMEM 165的表达抑制，表明该家族成员之间的功能保守。对人细胞的膜片钳分析表明，TMEM 165的表达与Ca 2+离子转运有关。此外，TMEM 165中的缺陷影响Ca 2+和pH稳态。基于这些结果，我们提出，Gdt 1 p和TMEM 165可能是一个独特的高尔基体定位的Ca 2 +/H+反向转运蛋白家族的成员，高尔基体Ca 2+和pH平衡的修改可以解释TMEM 165缺陷患者中观察到的糖基化缺陷。
Defects in the human protein TMEM165 are known to cause a subtype of Congenital Disorders of Glycosylation. Transmembrane protein 165 (TMEM165) belongs to an uncharacterized family of membrane proteins called Uncharacterized Protein Family 0016, which are well conserved throughout evolution and share characteristics reminiscent of the cation/Ca2+ exchanger superfamily. Gcr1 dependent translation factor 1 (Gdt1p), the budding yeast member of this family, contributes to Ca2+ homeostasis via an uncharacterized Ca2+ transport pathway localized in the Golgi apparatus. The gdt1 Delta mutant was found to be sensitive to high concentrations of Ca2+, and interestingly, this sensitivity was suppressed by expression of TMEM165, the human ortholog of Gdt1p, indicating conservation of function among the members of this family. Patch-clamp analyses on human cells indicated that TMEM165 expression is linked to Ca2+ ion transport. Furthermore, defects in TMEM165 affected both Ca2+ and pH homeostasis. Based on these results, we propose that Gdt1p and TMEM165 could be members of a unique family of Golgi-localized Ca2+/H+ antiporters and that modification of the Golgi Ca2+ and pH balance could explain the glycosylation defects observed in TMEM165-deficient patients.