MENTHO, a MLN64 homologue devoid of the START domain
MENTHO, a MLN64 homologue devoid of the START domain
复制标题
DOI：
10.1074/jbc.m208290200
复制
发表时间：
2002-12-27
影响因子：
4.8
通讯作者：
Tomasetto, C
中科院分区：
文献类型：
--
作者：
Alpy, F;Wendling, C;Tomasetto, C
MLN64 是一种晚期内体膜蛋白，含有羧基末端胆固醇结合 START 结构域，可能参与细胞内胆固醇转运。在本研究中，我们克隆了编码一种新蛋白的人类 cDNA，我们将其称为 MENTHO，是 MLN64 N 端结构域同源物的首字母缩写，因为该蛋白与 MLN64 的氨基端部分密切相关。 MLN64 和 MENTHO 在包含 171 个氨基酸的原始蛋白质结构域中具有 70% 的同一性和 83% 的相似性，我们将其指定为 MENTAL（MLN64 N 端）结构域。通过翻译起始扫描，MENTHO 被合成为可磷酸化的 234 (α) 和 227 (β) 氨基酸的两种亚型。与 MLN64 一样，MENTHO 广泛表达并位于晚期内涵体的膜中，其氨基和羧基末端末端伸向细胞质。我们表明，MENTHO 过度表达并不能挽救 Niemann-Pick C 型脂质储存表型。然而，MENTHO 过度表达会导致稳定状态下扩大的内体积累，从而严重改变内吞区室。这些结果表明，除了先前确定的将蛋白质定位和锚定到晚期内涵体膜上的功能之外，MENTAL 结构域还具有内吞转运中的内在生物学功能。
MLN64 is a late endosomal membrane protein containing a carboxyl-terminal cholesterol binding START domain and is presumably involved in intracellular cholesterol transport. In the present study, we have cloned a human cDNA encoding a novel protein that we called MENTHO as an acronym for MLN64 N-terminal domain homologue because this protein is closely related to the amino-terminal half of MLN64. MLN64 and MENTHO share 70% identity and 83% similarity in an original protein domain encompassing 171 amino acids that we designated as the MENTAL (MLN64 N-terminal) domain. By translation initiation scanning MENTHO is synthesized as two isoforms of 234 (alpha) and 227 (beta) amino acids that can be phosphorylated. As MLN64, MENTHO is ubiquitously expressed and is located in the membrane of late endosomes, its amino and carboxyl-terminal extremities projecting toward the cytoplasm. We show that MENTHO overexpression does not rescue the Niemann-Pick type C lipid storage phenotype. However, MENTHO overexpression alters severely the endocytic compartment by leading at steady state to the accumulation of enlarged endosomes. These results indicate that in addition to its previously established function in addressing and anchoring proteins to the membrane of late endosomes, the MENTAL domain possesses an intrinsic biological function in endocytic transport.