Physiology & Biophysics

Mark D. Parker, PhD
Instructor
PhD, Biochemistry, University of Bristol Medical School
View Curriculum Vitae (pdf)


School of Medicine E552-D
10900 Euclid Ave
Cleveland, OH 44116-4970
Phone: 216-368-5530
Fax: 216-368-5586
mark.d.parker@case.edu

Research Interests

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

Specific Projects
  1. 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.

  2. 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.

Featured Publications
  • Parker MD, Qin X, Williamson RC, Toye AM, and Boron WF. HCO3--independent conductance with a mutant Na/HCO3 cotransporter (SLC4A4) in a case of proximal renal tubular acidosis with hypokalemic paralysis. J Physiol In press: 2012.
  • Lee S-K, Boron WF, and Parker MD. Relief of autoinhibition of the electrogenic Na/HCO3 cotransporter NBCe1-B: role of IRBIT versus amino-terminal truncation. Am J Physiol Cell Physiol 302: C518-C526, 2011.
  • 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.
Related Research Areas