Open AccessGenome-wide CRISPR screen reveals CLPTM1L as a lipid scramblase required for efficient glycosylphosphatidylinositol biosynthesis
Author(s) -
Yicheng Wang,
Anant K. Me,
Yuta Maki,
Yi-Shi Liu,
Yoshinobu Iwasaki,
Morihisa Fujita,
Paula A Guerrero,
Daniel Varón Silva,
Peter H. Seeberger,
Yoshiko Murakami,
Taroh Kinoshita
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2115083119
Subject(s) - phospholipid scramblase , endoplasmic reticulum , microbiology and biotechnology , biology , lipid bilayer , flippase , transmembrane protein , biosynthesis , membrane contact site , glycoconjugate , membrane protein , cytosol , diacylglycerol kinase , biochemistry , translocon , membrane lipids , integral membrane protein , phospholipid , membrane , signal transduction , phosphatidylserine , gene , enzyme , protein kinase c , receptor
Significance Scramblases translocate lipids across the lipid bilayer without consumption of ATP, thereby regulating lipid distributions in cellular membranes. Cytosol-to-lumen translocation across the endoplasmic reticulum (ER) membrane is a common process among lipid glycoconjugates involved in posttranslational protein modifications in eukaryotes. These translocations are thought to be mediated by specific ER-resident scramblases, but the identity of these proteins and the underlying molecular mechanisms have been elusive. Here, we show that CLPTM1L, an integral membrane protein with eight putative transmembrane domains, is the major lipid scramblase involved in efficient glycosylphosphatidylinositol biosynthesis in the ER membrane. Our results validate the long-standing hypothesis that lipid scramblases ensure the efficient translocations of lipid glycoconjugates across the ER membrane for protein glycosylation pathways.