TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine
| Autor: | Shiqian Qi, Elvis Pandzic, Sarah E. Hancock, Yvette Celine Aw, Anthony S. Don, Ivan Lukmantara, Renee Whan, Yang Emma Li, Yichang Wang, Ximing Du, Tizhong Zhang, Nigel Turner, Holly P. McEwen, Xiuju Dong, Hongyuan Yang, Hoi Yin Mak, Yiqiong Yuan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Phospholipid scramblase
Phosphatidylserines Biology Endoplasmic Reticulum Biochemistry Seipin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lipid droplet Report Autophagy Humans Integral membrane protein 030304 developmental biology Host factor 0303 health sciences Endoplasmic reticulum Membrane and Lipid Biology Autophagosomes Membrane Proteins COVID-19 Cell Biology Phosphatidylserine Lipid Droplets Cell biology Coronavirus Protein Transport Cholesterol chemistry lipids (amino acids peptides and proteins) Organelle biogenesis 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | The Journal of Cell Biology |
| Popis: | VMP1 and TMEM41B, integral membrane proteins of the ER, regulate the formation of autophagosomes, lipid droplets, and lipoproteins. Here, Li, Wang, et al. show that they have phospholipid scramblase activity, which is essential to the normal distribution of cholesterol and phosphatidylserine in mammalian cells. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|