CLPTM1L is a lipid scramblase involved in glycosylphosphatidylinositol biosynthesis

Author:

Wang YichengORCID,Menon Anant K.ORCID,Maki YutaORCID,Liu Yi-Shi,Iwasaki YugoORCID,Fujita MorihisaORCID,Guerrero Paula A.,Varón Silva Daniel,Seeberger Peter H.,Murakami YoshikoORCID,Kinoshita TarohORCID

Abstract

AbstractGlycosylphosphatidylinositols (GPIs) are membrane anchors of many eukaryotic cell surface proteins. Biosynthesis of GPIs is initiated at the cytosolic face of the endoplasmic reticulum (ER) and the second intermediate, glucosaminyl-phosphatidylinositol (GlcN-PI), is translocated across the membrane to the lumenal face for later biosynthetic steps and attachment to proteins. The mechanism of the lumenal translocation of GlcN-PI is unclear. We report that Cleft lip and palate transmembrane protein 1-like protein (CLPTM1L), an ER membrane protein of unknown function, is a lipid scramblase involved in GPI biosynthesis. Purified CLPTM1L scrambles GlcN-PI, PI, and several other phospholipids in vitro. Knockout of CLPTM1L gene in mammalian cultured cells partially decreased GPI-anchored proteins due to impaired usage of GlcN-PI, suggesting a major role of CLPTM1L in lumenal translocation of GlcN-PI.One-Sentence SummaryCLPTM1L translocates glucosaminyl-phosphatidylinositol across the membrane during glycosylphosphatidylinositol biosynthesis.

Publisher

Cold Spring Harbor Laboratory

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Essential roles of phosphatidylinositol 4-phosphate phosphatases Sac1p and Sjl3p in yeast autophagosome formation;Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids;2022-09

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