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Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism.


ABSTRACT: 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 Kif3a(?)(/flox) Pax8(Cre/)(+) mutant mice. Our results indicate first that 3-week-old Pax8(Cre/)(+) 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 Pax8(Cre/)(+) 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 any Pax8 gene alteration leads to altered G protein-coupled receptor plasma membrane expression, as shown for the ?2 adrenergic receptor, and we suggest that a similar mechanism may explain the altered TSH signaling and mild hypothyroidism detected in Kif3a(?)(/flox) Pax8(Cre/)(+) mutant mice.

SUBMITTER: D'Amico E 

PROVIDER: S-EPMC4404413 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism.

D'Amico Eva E   Gayral Stéphanie S   Massart Claude C   Van Sande Jacqueline J   Reiter Jeremy F JF   Dumont Jacques E JE   Robaye Bernard B   Schurmans Stéphane S  

Journal of molecular endocrinology 20130423 3


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 Kif3a(Δ)(/flox) Pax8(Cre/)(+) mutant mice. Our results indicate first that 3-week-old Pax8(Cre/)(+) mice us  ...[more]

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