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John Orlowski - Professor & Chair

Department of Physiology
McGill University
Room 1001
McIntyre Medical Sciences Building
3655 Promenade Sir William Osler
Montréal, Québec H3G 1Y6

(514) 398-8335

john [dot] orlowski [at] mcgill [dot] ca

Laboratory Web Site:
www.medicine.mcgill.ca/physio/orlowskilab

Research Area:  Cell and Molecular Biology

Research Description:

The research interests of my laboratory are to better understand the molecular mechanisms underlying pH homeostasis of mammalian cells, focusing on a certain family of transporters called sodium/proton exchangers.  In addition to regulating cytoplasmic and organellar pH, they play an important role in the maintenance of cell volume and the (re)absorption of sodium across intestinal and renal epithelial cells.  Abnormal expression of some of these transporters has been implicated in the pathogenesis of certain human diseases, including essential hypertension, congenital secretory diarrhea, and injuries resulting from episodes of cardiac ischemia and reperfusion

Education:  B.Sc., McGill, M.Sc., Ph.D., Queen's

Recent Publications:

Deane, E.C., Ilie, A.E., Sizdahkhani, S., Das Gupta, M., Orlowski, J. and McKinney, R.A. (2013) Enhanced recruitment of endosomal Na+/H+ exchanger NHE6 into dendritic spines of hippocampal pyramidal neurons during NMDA receptor-dependent long-term potentiation. J. Neurosci. 33: 595-610.

 Lukashova, V., Jinadasa, T., Ilie, A.E., Verbich, D., Cooper E. and Orlowski, J. (2013) The Na+/H+ exchanger NHE5 isoform is sorted to discrete intracellular vesicles in the central and peripheral nervous systems. Adv. Exp. Med. Biol. 961: 397-410.

 Zaun, H. C., Shrier, A., and Orlowski, J. (2012) N-myristoylation and Ca2+-binding of calcineurin B-homologous protein CHP3 are required to enhance Na+/H+ Exchanger NHE1 half-life and activity at the plasma membrane. J. Biol. Chem. 287(44):36883-95.

 Lukashova, V., Szabó, E.Z., Jinadasa, T., Mokhov, A., Litchfield, D.W. and Orlowski, J. (2011) CK2 Phosphorylation of an acidic Ser/Thr di-isoleucine motif in Na+/H+ exchanger NHE5 promotes association with β-arrestin2 and endocytosis.  J. Biol. Chem. 286(13):11456-11468.

 Alexander, R.T., Yeung, T., Furuya, W., Peltekova, I., Boucher, A., Zasloff, M., Orlowski, J. and Grinstein, S. (2011) Membrane surface charge dictates the structure and function of the epithelial Na+/H+ exchanger.  EMBO J.  30(4):679-691.

 Casey, J.R., Grinstein, S. and Orlowski, J. (2010) Sensors and regulators of intracellular pH. Nature Reviews Molecular Cell Biology 11(1):50-61.

 Kintner, D.B., Chen, X., Currie, J., Chanana, V., Ferrazzano, P., Chiu, S.-Y. , Baba, A., Matsuda, M., Cohen, M., Orlowski, J., Taunton, J., and Sun, D. (2010) Excessive Na+/H+ exchange in disruption of dendritic Na+ and Ca2+ homeostasis and mitochondrial dysfunction following in vitro ischemia. J. Biol. Chem. 285(45): 35155–35168.

 Zaun, H.C., Shrier, A. and Orlowski, J. (2008) Calcineurin B-homologous protein 3 promotes the biosynthetic maturation, cell surface stability and optimal transport of the Na+/H+ exchanger NHE1 isoform.   J. Biol. Chem. 283(18):12456-67.

 Alexander, R.T., Furuya, W., Szaszi, K., Orlowski, J., and Grinstein, S. (2005) Rho GTPases dictate the mobility of the Na+/H+ exchanger NHE3 in epithelia. Role in apical retention and targeting.  Proc. Natl. Acad. Sci. USA 102(34): 12253-12258.

 Lin, P. J. C., Williams, W. P., Luu, Y., Molday, R. S., Orlowski, J. and Numata, M. (2005) Secretory carrier membrane proteins interact and regulate trafficking of the organellar (Na+,K+)/H+ exchanger NHE7.  J. Cell Sci. 118: 1885-1897.

 Szabó, E.Z., Numata, M., Lukashova, V., Iannuzzi, P. and Orlowski, J. (2005) b-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform.  Proc. Natl. Acad. Sci. USA 102(8): 2790-2795.