Sodium-coupled bicarbonate transporters
Structure-function relationships of Na+-coupled HCO3- transporters (NCBTs) and molecular mechanisms of NCBT regulation by protein binding partners.
Stimulation of NCBT activity by cytosolic binding partners
Na+/HCO3- cotransport by the transmembrane domain (TMD) of Na+-coupled HCO3 transporters is stimulated by binding of IRBIT and, in the case of NBCn1, calcineurin (Cn) to the cytosolic Nt of the transporter
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.
Major Research Areas |
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Ion Channels, Membrane Trafficking, Protein-Protein Interactions, Renal Proximal Tubules, pH Regulation |
Disciplines |
Electrophysiology, Molecular Biology |
Organ Systems |
Nervous System, Renal System |
Diseases |
Acid-Base Disturbances, Channelopathies, Hypertension |
Major Techniques |
Electrophysiology, Ion Transport, Ion-Sensitive Microelectrodes, Protein Expression, Two-Electrode Voltage-Clamp Technique |