Maekawa Satoshi, Mori Daisuke, Nishiya Tadashi, Takikawa Osamu, Horinouchi Takahiro, Nishimoto Arata, Kajita Emi, Miwa Soichi
Department of Pharmacology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Biochim Biophys Acta. 2007 Jun;1773(6):1000-6. doi: 10.1016/j.bbamcr.2007.04.005. Epub 2007 Apr 19.
A novel organic cation transporter OCTN2 is indispensable for carnitine transport across plasma membrane and subsequent fatty acid metabolism in the mitochondria. Here, we report a novel splice variant of OCTN2 (OCTN2VT), in which a 72-base-pair sequence located in the first intron of OCTN2 gene was spliced between exons 1 and 2 of OCTN2, causing the insertion of 24 amino acids in the first extracellular loop of OCTN2. Despite the similarity between OCTN2 and OCTN2VT regarding primary structure and tissue distribution, their biochemical characteristics were significantly different. OCTN2 was expressed on the plasma membrane with robust N-glycosylation, whereas OCTN2VT was retained in the endoplasmic reticulum (ER) with poor N-glycosylation. In addition, the retention in the ER caused no carnitine uptake into the cells. These results demonstrate that the biochemical and functional characteristics of OCTN2VT are distinct from OCTN2 due to the insertion of 24 amino acids in the first extracellular loop.
一种新型有机阳离子转运体OCTN2对于肉碱跨质膜转运以及随后线粒体中的脂肪酸代谢不可或缺。在此，我们报告了OCTN2的一种新型剪接变体（OCTN2VT），其中位于OCTN2基因第一内含子的一段72个碱基对的序列被剪接到OCTN2的外显子1和外显子2之间，导致OCTN2的第一个细胞外环中插入了24个氨基酸。尽管OCTN2和OCTN2VT在一级结构和组织分布方面相似，但其生化特性却显著不同。OCTN2在质膜上表达且具有强大的N - 糖基化，而OCTN2VT在内质网（ER）中滞留且N - 糖基化较差。此外，在内质网中的滞留导致细胞无法摄取肉碱。这些结果表明，由于第一个细胞外环中插入了24个氨基酸，OCTN2VT的生化和功能特性与OCTN2不同。
