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Flip-flopping in plasma membrane


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Flip-flopping of lipids (and in proteins it is impossible) in plasma membrane is rare due to high energy barrier (video ref). However, it is an important mechanism since it allows asymmetric distribution of lipids in cell membrane.

Question: If a specific lipid is flipped E.g. phosphatidylinositol from cytoplasm side to extra-cellular side (E.g. by flippase), what mechanism can the cell do to ensure it will stay towards the extra-cellular fluid side but not flip-flop AGAIN (i.e. establish the asymmetry & enable its function)?




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I'm certainly not up on this subject, so please excuse my rudimentary knowledge. I also do not like answering a question with a question, why would a cell NOT want a phosphatidylinositol to return to the cytoplasm side? I mean isn't most flip-flopping necessary in the bilayer for cell growth or cell shape?


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The specific type of lipid may signal that a cell is undergoing apoptosis. 
Under normal conditions specific lipids are moved to either the outside or the inside of the cell, during apoptosis (and maybe other cell death inductions) a scrambling protein is activated. 

You may be interesting in those enzymes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613456/

for the more general mechanism https://pubmed.ncbi.nlm.nih.gov/28844836/ 

additional links that I just browsed through: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307283/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914033/

Hope that helps!

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