Regulation of heparan sulfate proteoglycan nuclear localization by fibronectin

Heparan sulfate proteoglycans (HSPG) regulate multiple cellular processes a nd mediate the cellular uptake of numerous molecules, While heparan sulphat e glycosaminoglycan chains are known to modulate receptor binding of severa l heparin-binding proteins, here we show that distinct extracellular matric es direct HSPG to, the nucleus. We analyzed HSPG localization in primary co rneal fibroblasts, cultured on fibronectin or collagen type I matrices, usi ng confocal laser scanning microscopy and cell fractionation, Image analysi s revealed that the nuclear localization of HSPG core proteins was greater when cells were cultured on fibronectin versus collagen. Matrices containin g the heparin-binding domain of fibronectin, but not the integrin-activatin g domain, demonstrated increased nuclear staining of core proteins. Further more, activation of protein kinase C with phorbol 12-myristate 13-acetate i nhibited nuclear targeting of HSPG in cells on fibronectin, whereas inhibit ion of protein kinase C with Ro-31-8220 greatly enhanced nuclear localizati on of HSPG in cells on both collagen and fibronectin, We propose a matrix-d ependent mechanism for nuclear localization of cell surface HSPG involving protein kinase C-mediated signaling. Nuclear localization of HSPG might pla y important roles in regulating nuclear function.