Tuesday, 09-Feb-2010 18:04:22 EST 		      The Structural Biology of Transporters and Channels
 





 


 


Welcome Message
Hello! We arrived from Yale University about two years ago. I miss the North East, especially Manhattan. But despite the blizzards in the cold winter, we thank the warm, laid-back welcome from the natives in Cleveland. We setup our labs and our resources for research in the Department of Physiology and Biophysics DPB within the School of Medicine at Case Western Reserve University CWRU. We extend our facilities and offer research collaborations to others investigators among the various departments at CWRU, the Cleveland Clinic, and anywhere for that matter. Read more at THE PEPCC


About my research: What are NCBTs?
Na+-coupled HCO3- transporters (NCBTs) are integral membrane proteins that play a vital role in transporting Na+ and HCO3- and Cl- in at least one case in tissues throughout the body. They represent at least half the ten-membered SLC4 family of HCO3- transporters. The SLC4 family can be divided into three major classes or groups based on their sequence homology. The first consists of the anion exchangers AE1-AE3. AE1, the founding member of the SLC4 family also known as band 3, was first cloned in 1985 from a spleen cDNA library by Kopito et al. One of the oldest-known transporters, AE1 is the Cl-HCO3 exchanger of erythrocytes and plays a key role in the delivery of CO2 from systemic tissues to the lung. The second group of SLC4 family members consists of three electroneutral, Na+-coupled HCO3- transporters: NBCn1, NDCBE, and NCBE. The Na+-driven Cl-HCO3 exchanger NDCBE plays a key role in the regulation of intracellular pH in neurons of the central nervous system. The third group of SLC4 members consists of the two electrogenic Na/HCO3 cotransporters NBCe1 and NBCe2. NBCe1 is present at the basolateral membrane of the proximal tubule, which reabsorbs 80% of the filtered HCO3-. This transporter completes the process of reabsorbing HCO3- from lumen to blood, thereby playing a critical role in the regulation of blood pH. Patients with defective NBCe1 have been diagnosed with mutations in NBCe1 that cause autosomal-recessive disorders that may include severe proximal renal tubular acidosis (pRTA), ocular abnormalities, and mental retardation. We use state-of-the-art methods to illuminate the molecular mechanisms of transport, including X-ray crystallography, multiangle-light scattering. We recombinantly generate large quantities (mg) of proteins using Escherichia coli and baculovirus expression systems.

NBCe1-Nt