Transbilayer phospholipid movement facilitates annexin 2 translocation across membranes
Journal of Cell Science
The Company of Biologists Ltd.
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Moreau, K., Stewart, S., Ashkenazi, A., Williamson, A., & Rubinsztein, D. Transbilayer phospholipid movement facilitates annexin 2 translocation across membranes. Journal of Cell Science, 131 1-12. https://doi.org/10.17863/CAM.27132
Annexins are cytosolic phospholipid binding proteins that can be found on the outer leaflet of the plasma membrane. Extracellular annexin functions include fibrinolysis activity and cell migration, among other functions. 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 show that the transbilayer movement of phospholipids facilitates the transport of annexins A2 and A5 across membranes in cells and in liposomes. We identified TMEM16F (anoctamin-6) 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.
This work was supported by Wellcome Trust Strategic Award [100574/Z/12/Z], MRC Metabolic Diseases Unit [MRC_MC_UU_12012/5], BBSRC Future Leader Fellowship (BB/P010911/1) and the Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge joint research grant for SES and KM, Wellcome Trust (Principal Research Fellowship to DCR (095317/Z/11/Z)), Strategic Grant to Cambridge Institute for Medical Research (100140/Z/12/Z), UK Dementia Research Institute (funded by the MRC, Alzheimer’s Research UK and the Alzheimer’s Society) (DCR), and by the Federation of European Biochemical Societies (FEBS Long-Term Fellowship) for AA.
Wellcome Trust (095317/Z/11/Z)
Wellcome Trust (100574/Z/12/Z)
This record's DOI: https://doi.org/10.17863/CAM.27132
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279762
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/