title: Effects of N-Glycosylation of the human cation channel TRPA1 on agonist-sensitivity.
abstract: Determining the functional significance of post-translational modifications advances our understanding of many broadly-expressed proteins, and particularly ion channels. The enzymes that catalyze these modifications are often expressed in a cell-type specific manner, resulting in considerable structural diversity among post-translationally modified proteins that are expressed across a variety of cell types. TRP channels exhibit notably variable behavior between cell types in vitro and in vivo , and they are frequently modified with N-glycans that contribute to protein function. TRPA1 possesses two putative N-linked glycosylation sites at N747 and N753 that have not yet been studied in detail. Here, we show that both of these sites can be modified with an N-glycan and that the glycan at position N747 modulates agonist-sensitivity of TRPA1 in vitro Additionally, we found that N-glycosylation also modulates cooperative effects of temperature and the agonist cinnamaldehyde on TRPA1 channel activation. Collectively, these findings suggest a dynamic role played by the N-glycosylation of human TRPA1. They also provide further evidence of the versatility of N-glycans and will assist in efforts to fully understand the complex regulation of TRPA1 activity.
authors: ETH Zürich, Zurich, Switzerland t.egan@numab.com.
authors: Timothy James
authors: TJ
authors: Egan
authors: Institute of Pharmacology & Toxicology, University of Zurich, Zurich, Switzerland.
authors: Mario A
authors: MA
authors: Acuña
authors: Cartilage Engineering & Regeneration Lab, the Department of Health, Science & Technology, ETH Zürich, Zurich, Switzerland.
authors: Marcy
authors: M
authors: Zenobi-Wong
authors: Institute of Pharmacology & Toxicology, University of Zurich, Zurich, Switzerland.
authors: Hanns Ulrich
authors: HU
authors: Zeilhofer
authors: Numab AG, Wädenswil, Switzerland.
authors: David
authors: D
authors: Urech
keywords: glycoproteins; glycosylation; ion channels; transient receptor potential channels