TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine

Yang Emma Li; Yichang Wang; Ximing Du; Tizhong Zhang; Hoi Yin Mak; Sarah E Hancock; Holly McEwen; Elvis Pandzic; Renee M Whan; Yvette Celine Aw; Ivan E Lukmantara; Yiqiong Yuan; Xiuju Dong; Anthony Don; Nigel Turner; Shiqian Qi; Hongyuan Yang

doi:10.1083/jcb.202103105

TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine

J Cell Biol. 2021 Jun 7;220(6):e202103105. doi: 10.1083/jcb.202103105.

Authors

Yang Emma Li^#¹, Yichang Wang^#², Ximing Du^#¹, Tizhong Zhang², Hoi Yin Mak¹, Sarah E Hancock³, Holly McEwen^{4

5}, Elvis Pandzic⁶, Renee M Whan⁶, Yvette Celine Aw¹, Ivan E Lukmantara¹, Yiqiong Yuan², Xiuju Dong², Anthony Don^{4

5}, Nigel Turner³, Shiqian Qi², Hongyuan Yang¹

Affiliations

¹ School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
² Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, College of Life Sciences, Sichuan University, Chengdu, China.
³ School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
⁴ Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.
⁵ National Health and Medical Research Council Clinical Trials Center, The University of Sydney, Camperdown, New South Wales, Australia.
⁶ Biomedical Imaging Facility, Mark Wainwright Analytical Center, New South Wales, Australia.

^# Contributed equally.

Abstract

TMEM41B and VMP1 are integral membrane proteins of the endoplasmic reticulum (ER) and regulate the formation of autophagosomes, lipid droplets (LDs), and lipoproteins. Recently, TMEM41B was identified as a crucial host factor for infection by all coronaviruses and flaviviruses. The molecular function of TMEM41B and VMP1, which belong to a large evolutionarily conserved family, remains elusive. Here, we show that TMEM41B and VMP1 are phospholipid scramblases whose deficiency impairs the normal cellular distribution of cholesterol and phosphatidylserine. Their mechanism of action on LD formation is likely to be different from that of seipin. Their role in maintaining cellular phosphatidylserine and cholesterol homeostasis may partially explain their requirement for viral infection. Our results suggest that the proper sorting and distribution of cellular lipids are essential for organelle biogenesis and viral infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagosomes*
Autophagy*
Cholesterol / metabolism*
Endoplasmic Reticulum / metabolism*
HeLa Cells
Humans
Lipid Droplets / metabolism
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Phosphatidylserines / metabolism*
Protein Transport

Substances

Membrane Proteins
Phosphatidylserines
TMEM41B protein, human
VMP1 protein, human
Cholesterol