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1989 M.D. Japan
1993 Ph.D. Japan
Tel: 604-822-7728
Email: mnumata@interchange.ubc.ca
Eukaryotic cells have various intracellular organelles with distinct functions that are segregated by organellar
membranes. Since organellar membranes, like the plasma membrane, are impermeable to ions, specialized membrane proteins
such as ion transporters, pumps and channels play vital roles in the ion homeostasis of intra-organellar spaces as well as
the cytosol.
Some proteins are targeted to multiple organelles before being delivered to their final destinations. For example,
certain proteins, after being synthesized, travel from the ER (endoplasmic reticulum) to the Golgi
apparatus, trans-Golgi network, secretory vesicles and eventually to the plasma membrane (secretory pathway). Furthermore, some
proteins in the plasma membrane are internalized to specialized vesicles, called endosomes, before reaching their final
location (endocytic pathway). The organellar pH along the secretory and endocytic pathways is tightly regulated, which is
important in protein targeting, receptor-ligand interaction, and enzymatic activities in the organelle. It has been also
suggested that impaired organellar pH may lead to cell death as well as unregulated proliferation and differentiation. However,
the precise molecular mechanism underlying how organellar pH homeostasis is achieved is not yet understood.
My research interest concerns how organellar pH is regulated under physiological and pathological conditions. The
Na+/H+ exchangers (NHEs) play pivotal roles in intracellular pH and cell volume regulation by their
transporter function, exchanging extracellular Na+ for intracellular H+. Originally, the NHEs were
identified in the plasma membrane as regulators of cytosolic pH. Recently, I have isolated human cDNAs encoding novel
NHE isoforms localizing to organellar membranes that are involved in maintaining organellar pH and ion homeostasis. We
will further characterize them by organellar ion flux assay and pH measurement in the presence of different pharmacological
inhibitors. In addition to these cell-based techniques, in vitro reconstitution systems in liposomes will be developed
for more precise functional analyses. We will also investigate NHE-interacting proteins through biochemical, cell
biological, genetic and immunological techniques. To further define biological roles of NHE proteins as well as the
interacting proteins, we are going to employ genetic approaches in different model-organism systems.
Caveolins bind to (Na + , K + )/H + exchanger NHE7 by a novel binding module
Lin, PJC., Williams, WP., Kobiljski, J., and Numata, M .
Cell Signal 19 978-988 (2007)
RACK1 associates with NHE5 and positively regulates the transporter activity”
Onishi, I. , Lin, P.J.C., Diering, G.H., Williams, W.P., and Numata, M.
Cell Signal 19 194-203 (2007)
Secretory Carrier Membrane Proteins interact and regulate the trafficking of the organellar Na + /H + exchanger NHE
Lin, P.J.C, Williams, W.P., Luu, Y. , Molday, R.S., Orlowski, J., and Numata, M.
J. Cell Sci 118 1885-97 (2005)
b -Arrestins bind and decrease cell-surface abundance of the Na + /H + exchanger NHE5 isoform
Szabo, E.Z., Numata, M., Lukashova, V., Iannuzzi, P., Orlowski, J.
Proc. Natl . Acad. Sci. USA 102 2790-2795 (2005)
Clathrin-mediated endocytosis and recycling of the neural-specific Na + /H + exchanger NHE5 isoform: regulation by phosphatidylinositol 3'-kinase and the actin cytoskeleton
Szaszi, K., Paulsen, A., Szabo, E.Z., Numata, M ., Grinstein, S. and Orlowski, J.
J. Biol. Chem . 277 42623-42632 (2002)
Molecular cloning and characterization of a novel (Na + , K + )/H + exchanger localized to the trans -Golgi network
Numata, M. and Orlowski, J.
J. Biol. Chem . 276 17387-17394 (2001)
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