Analysis of the native quaternary structure of vanilloid receptor 1

Vanilloid receptor subtype I (VRI) is a ligand-gated channel that can be ac tivated by capsaicin and other vanilloids as well as by protons and heat. I n the present study, we have analyzed the oligomeric state of VR1. Co-immun oprecipitation of differently tagged VRI molecules indicated that VRI can f orm oligomers. Using two different heterologous VR1 expression systems as w ell as endogenous VRI expressed in dorsal root ganglion cells, we analyzed oligomer formation using perfluorooctanoic acid polyacrylamide gel electrop horesis. Results were confirmed both with chemical cross-linking agents as well as through endogenous cross-linking mediated by transglutaminase. Our results clearly show that VRI forms multimers in each of the expression sys tems with a homotetramer as a predominant form. The oligomeric structure of VR1 may contribute to the complexity of VRI pharmacology. Finally, differe nces in glycosylation between the systems were observed, indicating the nee d for caution in the use of the heterologous expression systems for analysi s of VRI properties.