Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism
| العنوان: | Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism |
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| المؤلفون: | Eva D’Amico, Stéphanie Gayral, Stéphane Schurmans, Jacqueline Van Sande, Jeremy F. Reiter, Claude Massart, Jacques Emile Dumont, Bernard Robaye |
| المصدر: | Journal of molecular endocrinology, vol 50, iss 3 |
| بيانات النشر: | Bioscientifica, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | medicine.medical_specialty, 1.1 Normal biological development and functioning, Cellular polarity, Clinical Sciences, Thyroid Gland, Kinesins, Thyrotropin, Biology, Kif3a, Article, thyroid, Paediatrics and Reproductive Medicine, Endocrinology & Metabolism, Mice, PAX8 Transcription Factor, Endocrinology, Hypothyroidism, Underpinning research, Internal medicine, medicine, 2.1 Biological and endogenous factors, genetically-modified mouse, Animals, Paired Box Transcription Factors, TSH signaling pathway, KIF3A, Veterinary Sciences, Aetiology, Receptor, Molecular Biology, Metabolic and endocrine, business.industry, Thyroid, Kinesin, Mice, Mutant Strains, Mutant Strains, molecular motor, medicine.anatomical_structure, Second messenger system, kinesin 2, Signal transduction, business, Intracellular, Signal Transduction |
| الوصف: | Kinesins, including the kinesin 2/KIF3 molecular motor, play an important role in intracellular traffic and can deliver vesicles to distal axon terminals, to cilia, to nonpolarized cell surfaces or to epithelial cell basolateral membranes, thus taking part in the establishment of cellular polarity. We report here the consequences of kinesin 2 motor inactivation in the thyroid of 3-week-old Kif3aΔ/floxPax8Cre/+mutant mice. Our results indicate first that 3-week-old Pax8Cre/+mice used in these experiments present minor thyroid functional defects resulting in a slight increase in circulating bioactive TSH and intracellular cAMP levels, sufficient to maintain blood thyroxine levels in the normal range. Second, Kif3a inactivation in thyrocytes markedly amplified the phenotype observed in Pax8Cre/+mice, resulting in altered TSH signaling upstream of the second messenger cAMP and mild hypothyroidism. Finally, our results in mouse embryonic fibroblasts indicate that Kif3a inactivation in the absence of anyPax8gene alteration leads to altered G protein-coupled receptor plasma membrane expression, as shown for the β2adrenergic receptor, and we suggest that a similar mechanism may explain the altered TSH signaling and mild hypothyroidism detected in Kif3aΔ/floxPax8Cre/+mutant mice. |
| وصف الملف: | application/pdf |
| تدمد: | 1479-6813 0952-5041 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b51841e6401280d32dd7b90f7549618fTest https://doi.org/10.1530/jme-12-0219Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b51841e6401280d32dd7b90f7549618f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14796813 09525041 |
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