Glycosylation of human receptor guanylyl cyclase C

Background Post translational modifications regulate several signalling pathways and glycosylation is emerging as a key player in this regulatory process. Glycosylation of cell surface receptors modulate the downstream signalling pathway and when altered causes a change in the normal physiology of the cell [1]. Guanylyl cyclase C (GC-C) belongs to a group of membrane bound receptors that produce the second messenger, cGMP [2]. It is a multidomain protein in which the extracellular domain (ECD) is N-glycosylated, resulting in the expression of two differentially glycosylated forms of GC-C (130 kDa and 145 kDa) [3]. Apart from the endogenous peptide ligands guanylin and uroguanylin, GC-C is activated by the heat stable enterotoxins (ST) produced by pathogenic Escherichia coli [2]. It is only the 145 kDa form which is activated by ST – a property attributed to the sugars present on it as both forms bind the ligand with comparable affinities as does the non-glycosylated ECD expressed in E. coli [4].