Genome-wide CRISPR screen reveals CLPTM1L as a lipid scramblase required for efficient glycosylphosphatidylinositol biosynthesis. Academic Article uri icon

Overview

abstract

  • SignificanceScramblases 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.

publication date

  • March 28, 2022

Research

keywords

  • Clustered Regularly Interspaced Short Palindromic Repeats
  • Glycosylphosphatidylinositols

Identity

PubMed Central ID

  • PMC9169118

Scopus Document Identifier

  • 85127262814

Digital Object Identifier (DOI)

  • 10.1073/pnas.2115083119

PubMed ID

  • 35344438

Additional Document Info

volume

  • 119

issue

  • 14