Sodium-coupled bicarbonate transporters
Structure-function relationships of Na+-coupled HCO3- transporters (NCBTs) and molecular mechanisms of NCBT regulation by protein binding partners.
Interactions between the cytosolic and transmembrane domains of NBCe1
The cytosolic amino terminal domain (Nt) of the electrogenic Na+/HCO3- cotransporter, NBCe1, exerts a stimulatory effect on the ion-transporting transmembrane domain (TMD). Even when expressed as separate fragments in the same cell, the Nt can still influence the activity of the TMD. We are investigating the reciprocal binding sites for the two domains as well as the mechanism(s) by which the Nt activates the TMD.
Stimulation of electroneutral Na+-coupled HCO3 transporters by protein binding partners
The three electroneutral Na/HCO3 cotransporters (NBCn1, NDCBE, and NBCn2) are abundantly expressed in neurons and in the epithelia of exocrine glands. HCO3- influx mediated by nNCBTs promotes neuronal excitability and also supports ion and fluid secretion by exocrine gland epithelia. All three transporters are stimulated by interaction of their Nt with the soluble protein IRBIT. NBCn1 is also stimluated by interaction of its Nt with calcineurin (Cn). We are investigating the mechanism(s) by which these binding partners stimulate HCO3- transport by NBCn1, NDCBE, and NBCn2.
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- Boron WF, Chen LM, and Parker MD. Modular Structure of Sodium-Coupled Bicarbonate Transporters. J Exp Biol 212: 1697-1706, 2009.
- Parker MD, Musa-Aziz R, Rojas JD, Choi I, Daly CM, and Boron WF. Characterization of human SLC4A10 as an electroneutral Na/HCO3 cotransporter (NBCn2) with Cl- self-exchange activity. J Biol Chem 283: 12777-12788, 2008.
- Parker MD, Ourmozdi EP, and Tanner MJ. Human BTR1, a new bicarbonate transporter superfamily member and human AE4 from kidney. Biochem Biophys Res Commun 282: 1103-1109, 2001.