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.
Kwon
Soojin
S
Department of Life Sciences, Division of Life and Pharmaceutical Sciences, The Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Daehyun-dong, Seodaemoon-Gu, Seoul 120-750, Republic of Korea.
Son
Hyowon
H
Choi
Youngsil
Y
Lee
Jung-Hyun
JH
Choi
Sojoong
S
Lim
Yangmi
Y
Han
Inn-Oc
IO
Oh
Eok-Soo
ES
D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004815:Epidermal Growth Factor / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D053671:Syndecan-4 / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D019269:Phosphatidylinositol 4,5-Diphosphate; D010743:Phospholipids; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D053671:Syndecan-4; D004815:Epidermal Growth Factor; D010738:Type C Phospholipases