Michael Jennings

Michael L. Jennings
Professor and Chair
Ph.D., Harvard University
Office: (501) 296-1438
Lab: (501) 296-1439

My research is focused on the structure, function, and regulation of ion transport proteins. For many years we used the red blood cell chloride-bicarbonate exchange protein known as AE1 as a model system for studying coupled ion transport.  Recently our interest shifted to a protein known as BTR1 that is related to AE1.  Mutations in BTR1 cause a human condition called CHED (congenital hereditary endothelial dystrophy) of the cornea, which results in cloudy vision.  BTR1 has been reported to be a boron transporter, but there is no direct evidence that it actually transports boron.  We are in the process of determining whether BTR1 transports boron (and if not, determine what it does transport) and are preparing a mouse model of human CHED to try to understand the pathophysiology of this condition.  This project is a collaboration with Mark D. Parker of Case Western Reserve University.

Another current interest is in hydrogen sulfide (H2S) and sulfide ion (HS) transport.   Although there is considerable evidence for the importance of H2S as a signaling molecule, until recently there were no measurements of H2S or HS transport through a mammalian cell membrane.  I measured the rates of dissipation of pH gradients across the human red blood cell membrane and found that these rates are strongly accelerated by sub-mM concentrations of H2S/HS .  With the help of some mathematical modeling, the pH transients were used to quantify the permeability of both H2S and HS.  Sulfide ion is transported rapidly by the chloride transporter AE1 (about 1/3 as rapidly as chloride), and H2S penetrates the membrane rapidly by either diffusing through the bilayer or through an aquaporin.  These measurements represent the first estimates of the permeation rates of H2S or HS across a mammalian cell membrane.

For the past several years we have been studying the regulation of S. cerevisiae sulfur assimilation with the goal of identifying a sensor for sulfate ion (none is known in any biological system).  We found that, surprisingly, the sulfate transport Sul2p is regulated not by sensing sulfate ion but by an intrinsic autoregulatory mechanism in the transporter itself, which causes the transporter to be degraded at a rate that is proportional to the rate at which the transporter is working.  There have been two other very recent examples of use-dependent transporter inactivation, which is a new mechanism of regulating ion transport.  Future studies will be aimed at determining the molecular origin of this autoregulation and in understanding other aspects of regulation of yeast S assimilation, including the question of why so little H2S is lost during S assimilation.

Current Grant Support

NIH 1R21 EY021646  Functional role of transporter SLC4a11 (BTR1/NaBC1) in the cornea.  12/01/2011-11/30/2013

PI: M. Jennings, Co-PI: M. Parker

Dr. Jennings’ Laboratory Homepage

Representative Publications

Jennings, M.L. 2013.  Transport of hydrogen sulfide and hydrosulfide anion across the human red blood cell membrane.  Rapid H2S diffusion and AE1-mediated Cl/HS exchange.  Am. J. Physiol. Cell Physiol. July 17 (Epub ahead of print).

Jennings, M.L., Cui, J.  2012.  Inactivation of Saccharomyces cerevisiae sulfate transporter Sul2p: Use it and lose it.  Biophysical Journal 102: 768-776.

Jennings, M.L., Cui, J. 2008.  Chloride homeostasis in Saccharomyces cerevisiae: High affinity influx, V-ATPase-dependent sequestration, and identification of a candidate Cl sensor.  J. Gen. Physiol. 131: 379-391.

Chernova, M.N., Stewart, A.K., Barry, P.N., Jennings, M.L., Alper S.L. 2008.  Mouse AE1 mutant E699Q mediates SO42-i/aniono exchange with reversed pHo sensitivity modulated by [SO42-]oAm. J. Physiology. Cell Physiol. 295: C302-C312.

Jennings, M.L., Howren T.R., Cui, J., Winters, M., Hannigan, R. 2007.  Transport and regulatory characteristics of the yeast bicarbonate transporter homolog Bor1p.  Am. J. Physiol. Cell Physiol. 293: C468-C476.

Link to Dr. Jennings at PubMed