Communication Between the Calcium and cAMP Pathways Regulate the Expression of the TSH Receptor: TRPC2 in the Center of Action

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 prod...

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Bibliographic Details
Published in:Molecular endocrinology (Baltimore, Md.) Md.), 2012-12, Vol.26 (12), p.2046-2057
Main Authors: Löf, Christoffer, Sukumaran, Pramod, Viitanen, Tero, Vainio, Minna, Kemppainen, Kati, Pulli, Ilari, Näsman, Johnny, Kukkonen, Jyrki P, Törnquist, Kid
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Cell Line
Cyclic AMP - metabolism
Extracellular Signal-Regulated MAP Kinases - metabolism
MAP Kinase Signaling System
Original Research
Protein Processing, Post-Translational
Rats
Receptors, Thyrotropin - metabolism
RNA Interference
RNA, Small Interfering
Thyroglobulin - metabolism
Thyroglobulin - secretion
Thyroid Gland - cytology
Thyroid Gland - metabolism
TRPC Cation Channels - genetics
TRPC Cation Channels - metabolism
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Summary: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.
ISSN:0888-8809
1944-9917
DOI:10.1210/me.2012-1171