Abstract
The lipid phosphatidylinositol 4,5‐bisphosphate (PI(4,5)P2) has an important role in regulating membrane‐cytoskeleton‐adhesion and many other cellular processes. Although synthesis and degradation may locally regulate levels of PI(4,5)P2 in many cases, an alternative mechanism could be buffering by cationic proteins, like MARCKS . We found that increasing MARCKS protein levels by about 50% caused a decrease in membrane‐cytoskeleton adhesion by two‐fold, consistent with a drop in free PI(4,5) P2 levels. The drop in PI(4,5) P2 levels was reversed by over‐expression of phosphatidylinositol phosphate 5‐kinase type Iα (PIP5KIα) or by phosphorylation of MARCKS by PKC activation. Biochemical analyses of MARCKS‐/‐ fibroblasts showed elevated rates of turnover of both PI(4)P and PI(4,5)P2 as well as a decrease in PA turnover. Although total cellular level of PI(4,5)P2 did not change in MARCKS‐/‐ cells, the plasma membrane level of PI(4,5)P2 decreased by two fold, consistent with the loss of a buffer. All of these data suggest that there is compartmental regulation of PI(4,5)P2 in the cell that is not only controlled by the balance between synthesis and degradation, but also via sequestration by MARCKS protein.
Published Version
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