Naoto Hoshi

Picture of Naoto Hoshi
Associate Professor, Department of Pharmaceutical Sciences
School of Pharmacy & Pharmaceutical Sciences
Joint Appointment, Physiology and Biophysics
School of Medicine
M.D., Kanazawa University School of Medicine, Kanazawa, Japan., 1990
Ph.D., Kanazawa University Graduate School of Medicine, Kanazawa, Japan, 1999
Phone: (949) 824-0969
Fax: (949) 824-4855
University of California, Irvine
Pharm. Sci.
350C Med Surge 2
Mail Code: 4625
Irvine, CA 92697
Research Interests
Physiological role and regulation of the M-channel, molecular biology, electrophysiology and live cell FRET imaging
Academic Distinctions
2000, Juzen alumni award for young scientist
2004, Young scientist award from Uehara memorial foundation
2007, Juzen Medical award
Research Abstract
The Hoshi laboratory studies physiological role and regulation of the M-channel, a sub-threshold ion channel that regulates neuronal excitability. We have demonstrated that the AKAP150 macromolecular complex integrates multiple signals to regulate this channel. Genetic removal of AKAP150 resulted in tolerance to seizure induction. One of our goals is to control pathological neuronal activity through the M-channel modulators. The laboratory is now focused on understanding the physiological and pathological role of M-current suppression in learning and memory as well as in seizures. The laboratory utilizes molecular biology, electrophysiology, live cell FRET imaging and behavioral neuroscience.
Available Technologies
Hoshi, N., Zhang, J. S., Omaki, M., Takeuchi, T., Yokoyama, S., Wanaverbecq, N., Langeberg, L. K., Yoneda, Y., Scott, J. D., Brown, D. A., and Higashida, H. (2003). AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists. Nat. Neurosci. 6, 564-571.

Hoshi, N., Langeberg, L. K., and Scott, J. D. (2005). Distinct enzyme combinations in AKAP signalling complexes permit functional diversity. Nat. Cell Biol. 7, 1066-1073.
Above article was selected as “News & Views” in Nat. Cell Biol. and “This week in signal transduction” at Science’s STKE.

Bauman, A. L., Soughayer, J., Nguyen, B. T., Willoughby, D., Carnegie, G., K., Wong, W., Hoshi, N., Langeberg, L. K., Cooper, D.M.F., Dessauer, C. W. and Scott, J. D. (2006). Dynamic regulation of cAMP synthesis through anchored PKA- adenylyl cyclase V/VI complexes. Mol. Cell 23, 925-931.

Gold, M., G., Lygren, B., Dolurno, P., Hoshi, N., McConnachie, G., Taskén, K., Carlson, C. R., Scott, J. D., and Barford D. (2006) Molecular Basis of AKAP Specificity for PKA Regulatory Subunits. Mol. Cell 24, 383-395.

Saneyoshi, T., Wayman, G., Fortin, D., Davare, M., Hoshi, N., Nozaki, N., Natsume, T., Soderling, T. R. (2008) Activity-Dependent Synaptogenesis: Regulation by a CaM-Kinase Kinase/CaM-Kinase I/betaPIX Signaling Complex. Neuron 57, 94-107.

Tunquist, B. J.*, Hoshi, N*, Guire, E. S., Zhang, F, Mullendorff, K, Langeberg, L. K., Raber, J & Scott, J. D. (2008) Loss of AKAP150 perturbs distinct neuronal processes in mice. Proc. Natl. Acad. Sci. U S A 105, 12557-11262
* co-first authors

Hoshi, N, Langeberg, L. K., Gould, C. M., Newton, A. C., and Scott, J. D. (2010) Interaction with AKAP79 modifies the cellular pharmacology of PKC. Mol. Cell 37, 541-550.
Above article was selected for “preview” in Mol. Cell and as an “exceptional” article by Faculty of 1000 Biology.

Smith, I. M., Hoshi, N. (2011) ATP competitive Protein kinase C inhibitors demonstrate distinct state-dependent inhibition. Plos One 6, e26338.

Kosenko, A., Kang, S., Smith, I. M., Greene, D. Langeberg, L. K., Scott, J. D., & Hoshi, N (2012) Coordinated signal integration at the M-type potassium channel upon muscarinic stimulation EMBO J. 31, 3147-3156.
Above article is selected as a “recommended” article by Faculty of 1000 Biology.

Greene, D., Kang, S., Kosenko, A and Hoshi, N. (2012) Adrenergic regulation of HCN4 channel requires protein association with beta 2 adrenergic receptor J. Biol. Chem. 287, 23690-23697.

Nguyen, H. M., Miyazaki, H., Hoshi, N., Smith, B. J., Nukina, N., Goldin, A. L., and Chandy, K. G. (2012) Modulation of voltage-gated K+ channels by the sodium channel ß1 subunit PNAS. 109, 18577-18582 .
Above article is selected as a “recommended” article by Faculty of 1000 Biology.

Kosenko, A. and Hoshi, N. (2013) A Change in Configuration of the Calmodulin-KCNQ Channel Complex Underlies Ca2+-Dependent Modulation of KCNQ Channel Activity Plos One 8, e82290.

Kang, S., Xu, M., Cooper, E. C. and Hoshi, N. (2014) Channel anchored protein kinase CK2 and protein phosphatase 1 reciprocally regulate KCNQ2-containing M-channels via phosphorylation of calmodulin J. BIol. Chem. 289, 11536-11544.

Kay, HY, Greene, DL, Kang, S, Kosenko, A, Hoshi, N. (2015) M-current preservation contributes to anticonvulsant effects of valproic acid. J. Clin. Invest. 125, 3904-3914.

Jiang, L, Kosenko, A, Yu, C, Huang, L, Li, X, Hoshi, N. (2015) Activation of m1 muscarinic acetylcholine receptor induces surface transport of KCNQ channel via CRMP-2 mediated pathway. J. Cell Sci. 128,4235-4245.
Greene DL, Kang S, Hoshi N. (2017) XE991 and Linopirdine Are State-Dependent Inhibitors for Kv7/KCNQ Channels that Favor Activated Single Subunits. J Pharmacol Exp Ther. 362:177-185.
Smith FD, Omar MH, Nygren PJ, Soughayer J, Hoshi N, Lau HT, Snyder CG, Branon TC, Ghosh D, Langeberg LK, Ting AY, Santana LF, Ong SE, Navedo MF, Scott JD. (2018) Single nucleotide polymorphisms alter kinase anchoring and the subcellular targeting of A-kinase anchoring proteins. Proc Natl Acad Sci U S A. 115, E11465-E11474.
Greene DL, Kosenko, A, Hoshi, N. (2018) Attenuating M-current suppression in vivo by a mutant Kcnq2 gene knock-in reduces seizure burden and prevents status epilepticus-induced neuronal death and epileptogenesis. Epilepsia. 59, 1908-1918.
Kosenko A, Moftakhar S, Wood MA, Hoshi N. In vivo attenuation of M-current suppression impairs consolidation of object recognition memory. (2020) J. Neurosci. 40, 5847-5856.
National Institute of Neurological Disorders and Storke (NINDS) R01 NS067288, 01/15/10-11/30/15, $1,076,250 direct costs, Regulations and function of the M-channel (Role: P.I.).
Professional Societies
Society for Neuroscience (USA)
Japanese Neurochemistry Society (council member, 2000-presen
Japanese Biochemistry Society
Graduate Programs
Interdepartmental Neuroscience Program
Medicinal Chemistry and Pharmacology
Pharmacological Sciences
Last updated