The testis anion transporter TAT1 (SLC26A8) physically and functionally interacts with the cystic fibrosis transmembrane conductance regulator channel: a potential role during sperm capacitation.

[pendred syndrome]

The Slc 26 gene family encodes several conserved anion transporters implicated in human genetic disorders , including Pendred syndrome , diastrophic dysplasia and congenital chloride diarrhea . We previously characterized the TAT 1 (testis anion transporter 1 ; SLC 26 A 8 ) protein specifically expressed in male germ cells and mature sperm and showed that in the mouse , deletion of Tat 1 caused male sterility due to a lack of sperm motility , impaired sperm capacitation and structural defects of the flagella . Ca (2 +), Cl (-) and HCO (3 )(-) influxes trigger sperm capacitation events required for oocyte fertilization ; these events include the intracellular rise of cyclic adenosine monophosphate (cAMP ) and protein kinase A (PKA )-dependent protein phosphorylation . The cystic fibrosis transmembrane conductance regulator (CFTR ) is expressed in mature sperm and has been shown to contribute to Cl (-) and HCO (3 )(-) movements during capacitation . Furthermore , several members of the SLC 26 family have been described to form complexes with CFTR , resulting in the reciprocal regulation of their activities . We show here that TAT 1 and CFTR physically interact and that in Xenopus laevis oocytes and in CHO -K 1 cells , TAT 1 expression strongly stimulates CFTR activity . Consistent with this , we show that Tat 1 inactivation in mouse sperm results in deregulation of the intracellular cAMP content , preventing the activation of PKA-dependent downstream phosphorylation cascades essential for sperm activation . These various results suggest that TAT 1 and CFTR may form a molecular complex involved in the regulation of Cl (-) and HCO (3 )(-) fluxes during sperm capacitation . In humans , mutations in CFTR and /or TAT 1 may therefore be causes of asthenozoospermia and low fertilizing capacity of sperm .

Diseases
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Diseases presenting "preventing the activation of pka-dependent downstream phosphorylation cascades essential for sperm activation" symptom

pendred syndrome

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