Article (Scientific journals)
Thyroid-specific inactivation of Kif3a alters TSH signaling pathway and leads to hypothyroidism.
D'Amico, Eva; Gayral, Stéphanie; Massart, Claude et al.
2013In Journal of Molecular Endocrinology, 50, p. 375-387
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Keywords :
kinesin; thyroid; hypothyroidism
Abstract :
[en] Kinesins, including the kinesin 2/KIF3 molecular motor, play an important role in intracellular traffic and can deliver vesicles to distal axon terminal, to cilia, to non-polarized cell surface or to epithelial cell basolateral membrane, thus taking part to the establishment of cellular polarity. We report here the consequences of the kinesin 2 motor inactivation in the thyroid of 3 week-old Kif3a∆/flox Pax8Cre/+ 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 T4 levels in the normal range. Second, Kif3a inactivation in thyrocytes markedly amplified the phenotype observed in Pax8Cre/+ mice, resulting in an 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 any Pax8 gene alteration leads to altered GPCR plasma membrane expression, as shown for the β2 adrenergic receptor, and we suggest that a similar mechanism may explain the altered TSH signaling and mild hypothyroidism detected in Kif3a∆/flox Pax8Cre/+ mutant mice.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
D'Amico, Eva
Gayral, Stéphanie
Massart, Claude
Van Sande, Jacqueline
Reiter, Jeremy F
Dumont, Jacques
Robaye, Bernard
Schurmans, Stéphane  ;  Université de Liège - ULiège > Département de sciences fonctionnelles > Biochimie métabolique vétérinaire
Language :
Title :
Thyroid-specific inactivation of Kif3a alters TSH signaling pathway and leads to hypothyroidism.
Publication date :
Journal title :
Journal of Molecular Endocrinology
Publisher :
Society for Endocrinology, Bristol, United Kingdom
Volume :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
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since 19 March 2013


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