Christian Lytle
Associate Professor of Biomedical Sciences
|
Biomedical Research Signal Transduction
Ph.D., Duke University, 1988
VOICE: 951-827-2592 |
Our research focuses on three fundamental questions in cellular physiology:
1. How do animal cells perceive and control their volume? We investigate the mechanisms by which cells sense osmotic perturbations and then activate membrane transporters that restore cell volume. Current work focuses on a protein kinase cascade that activates the Na-K-2Cl cotransporter in response to cell shrinkage. Using a blend of biochemical, physiological, and genetic approaches, we seek information on the elements within this cascade which detect and transduce the volume stimulus. Of special interest are the roles of macromolecular crowding and chloride in cell volume perception.
2. What functions do basilar parietal cells serve in gastric fluid and acid secretion? Although it is now axiomatic that parietal cells secrete hydrochloric acid, a growing body of evidence indicates that these cells undergo major morphological and biochemical changes as they migrate from the isthmus to the base of the gastric gland. Our work suggests that parietal cells undergo a programmed conversion of their principal function from acid (HCl) secretion to fluid (NaCl or KCl) secretion on migrating into the base of the gland. The process of reconfiguration involves acquisitions and losses of several key transport proteins. We are using an immunocytochemical approach to identify these changes in relation to parietal cell age and spatial position within the gland. To clarify the functional consequences of this reconfiguration, H+ and Cl- transport by individual parietal cells inhabiting different levels of the gastric gland is being characterized by microspectrofluorometric analysis.
3. What is the nature of intestinal epithelial remodeling in inflammatory bowel disease, and what are the pathophysiological consequences of these alterations on intestinal fluid and electrolyte absorption and secretion?
Immunofluorescence localization of chloride transporters in rat gastric mucosa. Parietal cells abruptly express Na-K-2Cl cotransporter-1 protein on migrating down into neck of the gastric gland (Panel B, green). In contrast, upwardly-migrating parietal cells express Cl/HCO3 exchanger-2 (Panel C, green) (see McDaniel & Lytle, Am. J. Physiol. 276: G1273, 1999).
SELECTED PUBLICATIONS
Lytle, C., and T.J. McManus (2002) Coordinate modulation of Na-K-2Cl cotransport and K-Cl cotransport by cell volume and chloride. Am. J. Physiol. 283:C1422-C1431.
Roig, J,, Huang, Z., Lytle, C., and J.A. Traugh (2000) P21-activated protein kinase g-PAK is translocated and activated in response to hyperosmolarity. J. Biol. Chem. 275:16933-16940.
McDaniel, N., and C. Lytle (1999) Parietal cells express high levels of Na-K-2Cl cotransporter on migrating into the gastric gland neck. Am. J. Physiol. 276: G1273-G1280.
Lytle, C., McManus, T.J. and Haas, M. A model of Na-K-2Cl cotransport based on ordered ion binding and glide symmetry. Am. J. Physiol. 274:C299-C309 (1998).
Lytle, C. A volume-sensitive protein kinase regulates the Na-K-2Cl cotransporter in duck red cells. Am. J. Physiol. 274:C1002-C1010 (1998).
Lytle, C. Activation of the avian erythrocyte Na-K-Cl cotransport protein by cell shrinkage, cAMP, fluoride, and caylculinA involves phosphorylation at common sites. J. Biol. Chem. 272:15069-15077 (1997).
Lytle, C., Xu, J-.C., Biemesderfer, D. and Forbush III, B. Distribution and diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies. Am. J. Physiol. 269:C1496-C1505 (1995).
Lytle, C. and Forbush III, B. Regulatory phosphorylation of the secretory Na-K-CI cotransport protein: Modulation by cytoplasmic chloride. Am. J. Physiol. 270:C437-C448 (1995).
Xu, J.-C., Lytle, C., Zhu, T., Payne, J. and Forbush III, B. Molecular cloning and functional expression of the bumetanide-sensitive Na-K-CI cotransporter. Proc. Natl. Acad. Sci. 91:2201-2205 (1994).