Possible roles of sphingolipids in clathrin-mediated endocytosis - Vesicle formation by a glycerophospholipid cycle - a hypothesis
The participation of sphingolipids in non-clathrin-dependent endocytosis has been known for some time. The participation of sphingolipids in clathrin-mediated endocytosis (uptake of transferrin) has only recently been reported. It was shown that not only does the synthesis of sphingolipids play a significant role in clathrin-mediated endocytosis but also the degradation of sphingolipids. Thus, a cycling process seems likely and may suggest a role of lipids in creating vesicles whereas the current discussion gives curvature-inducing and -sensing proteins the leading role in this process.
We present a hypothetical cycle in which serine of phosphatidylserine and 2n-fatty acids of various glycerophospholipids are substrates for sphingolipid synthesis (sphingomyelin). Subsequently, sphingomyelin is broken down via acid sphingomyelinase, ceramidase, sphingosine-1-kinase and sphingosine-1-phosphate lyase. Phosphoethanolamine originating from the last reaction can be used for phosphatidylethanolamine synthesis. Phosphatidylserine synthase changes the head group of phosphatidylethanolamine to yield phosphatidylserine. Thus the original glycerophospholipids are restored.
It is likely that the particular metabolites not only have a physical role but also a role as signal molecules activating step by step the subsequent reaction in the developing vesicle and deactivating the previous one. That means that it is very difficult to measure the only temporarily activated enzymes. In order to prove this hypothesis it is initially important to search for the particular enzyme protein in the coated pit or vesicle independent of its activity. As the clathrin-mediated endocytosis is a fundamental process of all cells and is also involved in various diseases we should understand it not only for theoretical but also for medical reasons
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Approved by the authors 2012.
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