Engel Thomas, Bode Guenther, Lueken Aloys, Knop Markus, Kannenberg Frank, Nofer Jerzy-Roch, Assmann Gerd, Seedorf Udo
Leibniz Institute of Arteriosclerosis Research, Westphalian Wilhelms-University, Domagkstr. 3, 48149 Muenster, Germany.
FEBS Lett. 2006 Aug 7;580(18):4551-9. doi: 10.1016/j.febslet.2006.07.006. Epub 2006 Jul 13.
The ATP-binding cassette transporter ABCG1 mediates the transport of excess cholesterol from macrophages and other cell types to high density lipoprotein (HDL) but not to lipid-depleted apolipoprotein AI. Several splice variants which may have different functions have been identified in mammals. In the current study, we characterized the human splice variant ABCG1(666), which differs from full-length ABCG1(678) by absence of an internal segment of 12 amino acids (VKQTKRLKGLRK). Accordingly spliced ABCG1 transcripts were detected in macrophages and liver in approximately twofold higher amounts than the alternatively spliced ABCG1 form encoding full-length ABCG1. We used transient and stable expression of ABCG1(666) fusion proteins to characterize glycosylation, subcellular localization, molecular interaction and functions of this ABCG1 variant. It could be demonstrated that ABCG1(666) is located at the cell surface and has the ability to form cholesterol transport competent homodimers which affect cellular cholesterol export in a similar manner as previously characterized forms of ABCG1. Our results support that ABCG1(666) may in fact be the most prominent form of functional ABCG1 expressed in the human.
ATP结合盒转运蛋白ABCG1介导巨噬细胞和其他细胞类型中过量胆固醇向高密度脂蛋白（HDL）的转运，但不向脂质耗尽的载脂蛋白AI转运。在哺乳动物中已鉴定出几种可能具有不同功能的剪接变体。在本研究中，我们对人类剪接变体ABCG1(666)进行了表征，它与全长ABCG1(678)的不同之处在于缺少一段12个氨基酸的内部片段（VKQTKRLKGLRK）。在巨噬细胞和肝脏中检测到的相应剪接的ABCG1转录本的量比编码全长ABCG1的选择性剪接ABCG1形式高出约两倍。我们使用ABCG1(666)融合蛋白的瞬时和稳定表达来表征这种ABCG1变体的糖基化、亚细胞定位、分子相互作用和功能。可以证明ABCG1(666)位于细胞表面，并且有能力形成具有胆固醇转运能力的同源二聚体，其影响细胞胆固醇输出的方式与先前表征的ABCG1形式类似。我们的结果支持ABCG1(666)实际上可能是人类中表达的功能性ABCG1的最主要形式。
