John H. Schwartz, M.D.

Professor

Education:

M.D., New York University School of Medicine

General field of research:

Renal epithelial cell biology, ion transport

Affiliations other than medicine:

Evans Center for Interdisciplinary Biomedical Research

Contact information:

Office
EBRC, Rm 545
Phone: 617-638-7321

Lab
EBRC, Rm 540
Phone: 617-638-7330
Fax: 617-638-7326

jhsch@bu.edu

Research group information

Guneet Gochar, Graduate Student, gkochar@bu.edu

Vikram Suri,  Graduate student, vsuri@bu.edu

Giangmu Li, MD, Reserach Associate, guangmuli@verizon.net

Keywords:

Aquaporin-2, H+-ATPase, Snare, exocytosis, trafficking

Summary of research interest:

IMCD cells in vivo and in culture secrete H+, mediated by an H+-ATPase, and absorb H2O mediated by aquaporin-2  (AQP2).  In cultured rat IMCD cells and in intact IMCD segments, transport is regulated by SNARE mediated exocytic insertion and endocytic retrieval of vesicles carrying either the H+-ATPase or AQP2.  Although exocytosis of H+-ATPase and AQP2 are independently regulated, they utilize a similar SNARE system for membrane targeting-fusion.

Our studies will characterize the targeting process for these proteins and identify the disparate effects of SNARE regulators on H+-ATPase versus AQP2 membrane cycling. We will test the hypothesis that the B1 subunit of the plasma membrane H+-ATPase contains molecular information for targeting of the assembled H+-ATPase to the apical membrane.  B1 is the isoform of the B subunit that is present in the H+-ATPase of cells specialized for proton secretion. The other isoform,  B2, is present in the vesicula  r membrane H+-ATPase of all cells.

We predict that the targeting information for the plasma membrane H+-ATPase is encoded in either the N or the C-terminal amino acids, the two regions of ATP6V1B1 that are most dissimilar from B2.  Our studies will also determine the role of Munc 18-2 and snapin as SNARE regulators for H+-ATPase and AQP2.

Recent publications:

Nicoletta JA, Ross JJ, Li G, Cheng Q, et al. Munc-18-2 regulates exocytosis of H(+)-ATPase in rat inner medullary collecting duct cells. Am J Physiol Cell Physiol 2004; 287: C1366-1374. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15240346

Li G, Yang Q, Alexander EA, and Schwartz JH. Syntaxin 1A has a specific binding site in the H3 domain that is critical for targeting of H+-ATPase to apical membrane of renal epithelial cells. Am J Physiol Cell Physiol 289: C665-672, 2005. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15872013

Ruchalski KL, Mao H, Li Z, Wang Z, Gillers S, Wang Y, Mosser DD, Gabai V, Schwartz JH, and Borkan SC. Distinct Hsp70 domains mediate apoptosis inducing factor release and nuclear accumulation. J Biol Chem 281:7873-7880, 2006. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16407317

Li, G, Yang, Q, Krishnan, S, Alexander, EA, Borkan, SC & Schwartz, JH: A novel cellular survival factor – the B2 subunit of vacuolar H+-ATPase inhibits apoptosis. Cell Death Differ 13:2109-2117, 2006 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16710359

Yang, Q, Li, G, Singh, SK, Alexander, EA & Schwartz, JH: Vacuolar H+-ATPase B1 Subunit Mutations that Cause Inherited Distal Renal Tubular Acidosis Affect Proton Pump Assembly and Trafficking in Inner Medullary Collecting Duct Cells. J Am Soc Nephrol 17:1858-1866, 2006. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16769747

Schwartz JH, Li G, Yang Q, V Suri, J J Ross and E A Alexander.: Role of SNAREs and H(+)-ATPase in the targeting of proton pump-coated vesicles to collecting duct cell apical membrane. Kidney Int 72: 1310-1315, 2007. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17805241

Andrea Havasi, Zhijian Li, Zhiyong Wang, Jody L. Martin, Venugopal Botla, Kathleen Ruchalski, John H. Schwartz, and Steven C. Borkan. Hsp27 Inhibits Bax Activation and Apoptosis via a Phosphatidylinositol 3-Kinase-dependent Mechanism J. Biol. Chem283: 12305 -1231, 2008. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18299320

Technologies available for sharing upon request:

1)    Isolation of apical plasma membrane of epithelial cells
2)    Determination of Intracellular pH
3)    Transepithelial resistance of and electrical potential difference across cultured cells