Elucidation of the mechanism of intracellular phosphatidylinositol trafficking by the Phs1 family

ph1是一种3-羟基酰基辅酶a脱水酶，参与超长链脂肪酸（VLCFAs）的延伸。我们在这里证明了Phs1通过与参与脂质代谢和囊泡运输的蛋白质相互作用调节鞘脂合成和磷脂酰肌醇运输。我们还成功地鉴定了Phs1， HACD1-4的哺乳动物同源物。通过揭示催化VLCFA延伸限速步骤的酶的底物特异性，我们已经阐明了哺乳动物VLCFA的整个途径。此外，我们还了解了VLCFA延伸与某些疾病的关系。

Phs1 is a 3-hydroxyacyl-CoA dehydratase involved in the elongation of very long-chain fatty acids (VLCFAs). We demonstrated here that Phs1 regulates sphingolipid synthesis and phosphatidylinositol transport through interacting with proteins involved in lipid metabolism and vesicular transport. We also succeeded in identifying mammalian homologs of Phs1, HACD1-4. By revealing substrate specificities of enzymes catalyzing the rate-limiting step of the VLCFA elongation, we have elucidated the entire VLCFA pathways in mammals. Moreover, we obtained some knowledge about relationship between VLCFA elongation and certain disorders.