PMID: 12063277

 

    Legend: Sugar

Title : Role of glycosylation in cell surface expression and stability of HERG potassium channels

Abstract :

1. The human ether-à-go-go-related gene ( HERG ) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel in the heart
2. We previously showed that HERG channel protein is modified by N-linked glycosylation
3. HERG protein sequence contains two extracellular consensus sites for N-linked glycosylation ( N598, N629 )
4. In this study, we used the approaches of site-directed mutagenesis and biochemical modification to inhibit N-linked glycosylation and studied the role of glycosylation in the cell surface expression and turnover of HERG channels
5. Our results show that N598 is the only site for N-linked glycosylation and that glycosylation is not required for the cell surface expression of functional HERG channels
6. In contrast, N629 is not used for glycosylation, but mutation of this site (N629Q) causes a protein trafficking defect, which results in its intracellular retention
7. Pulse-chase experiments show that the turnover rate of nonglycosylated HERG channel is faster than that of the glycosylated form, suggesting that N-linked glycosylation plays an important role in HERG channel stability