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

Although phosphatidylinositol 4,5-bisphosphate (PIP(2)) regulates syndecan-4 function, the potential influence of syndecan-4 on PIP(2) remains unknown. GFP containing PIP(2)-binding-PH domain of phospholipase Cdelta (GFP-PHdelta) was used to monitor PIP(2). Syndecan-4 overexpression in COS-7 cells enhanced membrane translocation of GFP-PHdelta, while the opposite was observed when syndecan-4 was knocked-down. PIP(2) levels were higher in total phospholipids extracted from rat embryo fibroblasts expressing syndecan-4. Syndecan-4-induced membrane targeting of GFP-PHdelta 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-PHdelta 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 PIP(2) by negatively regulating PLC-dependent PIP(2) degradation.