Syndecan-4 promotes the retention of phosphatidylinositol 4,5-bisphosphate in the plasma membrane

Although phosphatidylinositol 4,5-bisphosphate (PIP2) regulates syndecan-4 function, the potential influence of syndecan-4 on PIP2 remains unknown. GFP containing PIP2-binding-PH domain of phospholipase C delta (GFP-PH delta) was used to monitor PIP2. Syndecan-4 overexpression in COS-7 cells enhanced membrane translocation of GFP-PH delta, while the opposite was observed when syndecan-4 was knocked-down. PIP2 levels were higher in total phospholipids extracted from rat embryo fibroblasts expressing syndecan-4. Syndecan-4-induced membrane targeting of GFP-PH delta was further enhanced by phosphoinositide-3-kinase inhibitor, but not by phospholipase C (PLC) inhibitor. Besides, both ionomycin and epidermal growth factor caused dissociation of GFP-PH delta from plasma membrane, an effect that was significantly delayed by syndecan-4 over-expression. Collectively, these data suggest that syndecan-4 promotes plasma membrane retention of PIP2 by negatively regulating PLC-dependent PIP2 degradation. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.