title: Communication between the calcium and cAMP pathways regulate the expression of the TSH receptor: TRPC2 in the center of action.
abstract: Transient receptor potential (TRP) cation channels are widely expressed and function in many physiologically important processes. Perturbations in the expression or mutations of the channels have implications for diseases. Many thyroid disorders, as excessive growth or disturbed thyroid hormone production, can be a result of dysregulated TSH signaling. In the present study, we found that of TRP canonicals (TRPCs), only TRPC2 was expressed in Fischer rat thyroid low-serum 5% cells (FRTL-5 cells). To investigate the physiological importance of the channel, we developed stable TRPC2 knockdown cells using short hairpin RNA (shTRPC2 cells). In these cells, the ATP-evoked entry of calcium was significantly decreased. This led to increased cAMP production, because inhibitory signals from calcium to adenylate cyclase 5/6 were decreased. Enhanced cAMP signaling projected to Ras-related protein 1-MAPK kinase 1 (MAPK/ERK kinase 1) pathway leading to phosphorylation of ERK1/2. The activated ERK1/2 pathway increased the expression of the TSH receptor. In contrast, secretion of thyroglobulin was decreased in shTRPC2 cells, due to improper folding and glycosylation of the protein. We show here a novel role for TRPC2 in regulating thyroid cell function.
authors.affiliation: Department of Biosciences, Åbo Akademi University, Biocity, Tykistökatu 6A, 20520 Turku, Finland.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Löf
authors.forename: Pramod
authors.initials: P
authors.lastname: Sukumaran
authors.forename: Tero
authors.initials: T
authors.lastname: Viitanen
authors.forename: Minna
authors.initials: M
authors.lastname: Vainio
authors.forename: Kati
authors.initials: K
authors.lastname: Kemppainen
authors.forename: Ilari
authors.initials: I
authors.lastname: Pulli
authors.forename: Johnny
authors.initials: J
authors.lastname: Näsman
authors.forename: Jyrki P
authors.initials: JP
authors.lastname: Kukkonen
authors.forename: Kid
authors.initials: K
authors.lastname: Törnquist
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D011989:Receptors, Thyrotropin; D050052:TRPC Cation Channels; C491857:Trpc2 protein, rat; D013954:Thyroglobulin; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium