期刊
JOURNAL OF CELL SCIENCE
卷 131, 期 14, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.217034
关键词
TMEM16F; Lipid flipping; Protein translocation; Annexin
类别
资金
- Wellcome Trust [100574/Z/12/Z, 095317/Z/11/Z]
- Medical Research Council Metabolic Diseases Unit [MRC_MC_UU_12012/5]
- Biotechnology and Biological Sciences Research Council Future Leader Fellowship [BB/P010911/1]
- Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge joint research grant
- UK Dementia Research Institute - MRC
- UK Dementia Research Institute - Alzheimer's Research UK
- UK Dementia Research Institute - Alzheimer's Society
- Federation of European Biochemical Societies (FEBS Long-Term Fellowship)
- [100140/Z/12/Z]
- BBSRC [BB/P010911/1] Funding Source: UKRI
- MRC [MC_UU_12012/5, MC_UU_12012/1, MC_UU_00014/5, UKDRI-2002] Funding Source: UKRI
Annexins are cytosolic phospholipid-binding proteins that can be found on the outer leaflet of the plasma membrane. The extracellular functions of annexin include modulating fibrinolysis activity and cell migration. Despite having well-described extracellular functions, the mechanism of annexin transport from the cytoplasmic inner leaflet to the extracellular outer leaflet of the plasma membrane remains unclear. Here, we showthat the transbilayer movement of phospholipids facilitates the transport of annexins A2 and A5 across membranes in cells and in liposomes. We identified TMEM16F (also known as anoctamin-6, ANO6) as a lipid scramblase required for transport of these annexins to the outer leaflet of the plasma membrane. This work reveals a mechanism for annexin translocation across membranes which depends on plasma membrane phospholipid remodelling.
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