Question

Glypican is a heparin sulfate proteoglycan attached to the plasma membrane by a GPI anchor. Anyway, glypicans are actively involved in several transmembrane signaling processes. Describe a hypothetical mechanism by which glypican could direct transmembrane signaling

Answer 1

Glypicans are heparan sulfate proteoglycans that are bound to the outer surface of the plasma membrane by a glycosyl- phosphatidyl anchor. The main function is membrane attached glypicans is to regulate the cell signalling.

Depending on the biological context, glypicans can either stimulate or inhibit signalling activity. In the case of the stimulation of Wnut signalling, it has been proposed that the stimulatory mechanism is based on the ability of glypicans to facilitate and/or stabilize the interaction of wnuts with their signalling receptors, the frizzled proteins.

This hypothesis is based on the finding that glypicans can bind to wnuts and to frizzled and to transfection of glypicans increases the Wnut binding capacity of the transfected cells. In the case of Hhs, it has been recently reported that Gpc3 inhibits their signalling during development by competing with patched, the Hh receptor, for Hh binding. Because the HS chains have a strong negative charge, HS proteoglycans can interact in a rather promiscuous way with proteins that displays positively charged domains. On the basis it was originally thought that the HS chains were essential for glypicans activity. Indeed , this seems to be the case for the glypican- induced stimulation of FGF activity. The HS chains are only partially required for the regulatory activity of glypicans in Hh,Wnut,and BMP signalling. Furthermore , Hh has been shown to bind the core protein of GPC3 with high affinity.