Physiology and Pharmacology : Nikolai N. Modyanov

Professor Telephone: (419) 383-4182, 383-4065, 383-4456 FAX: (419) 383-2871 e-mail: Nikolai.Modyanov@utoledo.edu

Dr. Modyanov received a M.S. degree (Organic Chemistry, 1967) from the Lomonosov State University, Moscow, Russia; a Ph.D. degree (Bioorganic Chemistry, 1973) from the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (Moscow, Russia); and a D.Sc. degree (Chemistry, 1987) from the Russian Academy of Sciences. He joined the MUO faculty in 1994.

Research Interests:

• Since the early 1980's research in my lab is focused on the molecular aspects of ion transport across biological membranes, and primarily on the structure-function relationship of the ion-transporting ATPases that are receptors for cardiotonic drugs (Na,K-ATPase) and antiulcer drugs (H,K-ATPase).
• Together with colleagues we determined the complete primary structure of both subunits of Na,K-ATPase and discovered family of closely related human genes encoding different X,K-ATPases.  One of these genes (ATP1AL1) was shown to encode a catalytic subunit of a hitherto unknown human nongastric H,K-ATPase, which is a new type of human receptor for cardiac glycosides. The functional analysis of this novel human ion pump, which may play an important role in diverse cardiovascular and renal disorders linked to the dysfunction of ion homeostasis, is the major topic of the current studies.
• Another line of investigation resulted recently in discovery of a novel structural member of the mammalian X,K-ATPase ß-subunit gene family, designated as ßm due to its exclusive expression in skeletal and heart muscles. The ßm protein exhibits structural properties and cellular location, which are clearly distinct from those of the other X,K-ATPase ß-subunits. The studies are underway to elucidate functions of this hitherto unknown, muscle-specific protein.

Recent Publications:

• Ivanov, A., Zhao, H., and Modyanov, N.N. (2000) Packing of the transmembrane helices of Na,K-ATPase: Direct contact between beta-subunit and H8 segment of alpha-subunit revealed by oxidative cross-linking. Biochemistry:39:9778-9785.
• Crambert, G., Hasler,U., Beggah, A.T., Yu, C.L., Modyanov, N.N., Horisberger, J.D., Lelievre, L., and Geering, K. (2000) Transport and pharmacological properties of nine different human Na,K-ATPase isozymes. J. Biol. Chem. 275:1976-1986.
• Geering, K., Crambert, G., Yu, C., Korneenko, T.V., Pestov, N.B., and Modyanov, N.N. (2000) Role of membrane domains M9 and M10 in the assembly process and association efficiency of human, non-gastric H,K-ATPase alpha subunits (ATP1AL1) with known beta subunits. Biochemistry 39:12688-12698.
• Pestov, N.B., Korneenko, T.V., Zhao, H., Adams, G., Shakhparonov, M.I., and Modyanov, N.N. (2000) Immunochemical demonstration of a novel beta-subunit isoform of X,K-ATPase in human skeletal muscle. Biochem. Biophys. Res. Commun. 277:430-435.
• Adams, G., Tillekeratne, M., Yu, C., Pestov, N.B., and Modyanov, N.N. (2001) Catalytic function of nongastric H,K-ATPase expressed in Sf-21 insect cells. Biochemistry 40:5765-5776.
• Pestov, N.B., Korneenko, T.V., Zhao, H., Adams, G., Kostina, M.B., Shakhparonov, M.I., and Modyanov, N.N. (2001) The ßm protein, a member of the X,K-ATPase beta-subunits family, is located intracellularly in pig skeletal muscle. Arch. Biochem. Biophys.396:80-88.
• Pestov, N.B., Korneenko, T.V., Adams, G., Tillekeratne, M., Shakhparonov, M.I., and Modyanov, N.N. (2002) Nongastric H-K-ATPase in rodent prostate: lobe-specific expression and apical localization. Am. J. Physiol. Cell Physiol. 282:C907-C916.
• Ivanov, A., Modyanov, N.N., and Askari, A. (2002) Role of the self-association of beta subunits in the oligomeric structure of Na+/K+-ATPase. Biochem. J. 364:293-299.
• Crambert, G., Beguin, P., Pestov, N.B., Modyanov, N.N., and Geering, K. (2002) ßm, a structural member of the X,K-ATPase ß subunit family, resides in the ER and does not associate with any known X,K-ATPase alpha subunit. Biochemistry 41:6723-6733.
• Crambert, G., Horisberger, J-D., Modyanov, N.N., and Geering, K. (2002) Human nongastric H+-K+-ATPase: transport properties of ATP1al1 assembled with different beta-subunits. Am. J. Physiol. Cell. Physiol. 283:C305-C314.
• Modyanov, N., Pestov, N., Adams, G., Crambert, G., Tillekeratne, M., Zhao, H., Korneenko, T., Shakhparonov, M., and Geering, K. (2003) Nongastric H,K-ATPase: Structure and functional properties. Ann. N.Y. Acad. Sci. 986:183-187.
• Mobasheri, A., Pestov, N.B., Papanicolaou, S., Kajee, R., Cozar-Castellano, I., Avila, J., Martin-Vasallo, P., Foster, C.S., Modyanov, N.N., and Djamgoz, M.B. (2003) Expression and cellular localization of Na,K-ATPase isoforms in the rat ventral prostate. Brit. J. Urol. Int. 92:793-802.
• Pestov, N.B., Crambert, G., Zhao, H., Korneenko, T.V., Shakhparonov, M.I., Geering, K., and Modyanov, N.N. (2003) The muscle-specific beta-m protein is functionally different from other members of the X,K-ATPase beta-subunit family. Ann. N.Y. Acad. Sci. 986:304-305.
• Zhao, H., Pestov, N.B., Korneenko, T.V., Shakhparonov, M.I., and Modyanov, N.N. (2004) Accumulation of betaM, a structural member of X,K-ATPase beta-subunit family, in nuclear envelopes of perinatal myocytes. Am. J. Physiol. Cell. Physiol. 286:C757-C767.
• Pestov, N.B., Korneenko, T.V., Radkov, R., Zhao, H., Shakhparonov, M.I., and Modyanov, N.N. (2004) Identification of the beta-subunit for nongastric H,K-ATPase in rat anterior prostate. Am. J. Physiol. Cell. Physiol. 286:C1229-C1237.
• Pestov, N.B., Korneenko, T.V., Shakhparonov, M.I., Shull, G.E., and Modyanov, N.N. (2006) Loss of acidification of anterior prostate fluids in ATP12A null mutant mice indicates that the nongastric H,K-ATPase functions as a proton pump in vivo.  Am. J. Physiol. Cell Physiol., 291:C366-C374.
• Dmitriev RI, Korneenko TV, Bessonov AA, Shakhparonov MI, Modyanov NN, Pestov NB. (2007) Characterization of hampin/MSL1 as a node in the nuclear interactome.  Biochem Biophys Res Commun. Apr 20;355(4):1051-1057.
• Radkov R, Kharoubi-Hess S, Schaer D, Modyanov NN, Geering K, Horisberger JD. Role of homologous ASP334 and GLU319 in human non-gastric H,K- and Na,K-ATPases in cardiac glycoside binding. (2007) Biochem Biophys Res Commun. 2007 Apr 27;356(1):142-146.
• Pestov NB, Ahmad N, Korneenko TV, Zhao H, Radkov R, Schaer D, Roy S, Bibert S, Geering K, Modyanov NN.  (2007) Evolution of Na,K-ATPase beta m-subunit into a coregulator of transcription in placental mammals.  Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11215-11220.