Zhen Yan, Ph.D.
    

                         Professor
   

Research Interests:  

Mechanisms for the Regulation of Ligand-gated Ion Channels and Synaptic Transmission
     Information processing in the central nervous system (CNS) is achieved by the interplay between chemical and electrical signals. Neurotransmitters (e.g. serotonin, dopamine, acetylcholine) and hormones (e.g. corticosteroid) influence CNS functions by regulating ion channels, which can produce short-term changes in membrane excitability and long-term changes in synaptic plasticity. Dysfunctions of these neuromodulators in specific brain regions have been implicated in the pathogenesis of various mental disorders, including Schizophrenia, depression and Alzheimer’s disease. One of our major goals is to understand how these neuromodulators regulate ligand-gated ion channels and synaptic transmission in prefrontal cortex, a key region controlling cognition and emotion.
     Neuromodulators exert their actions through G protein-coupled receptors or nuclear hormone receptors. These receptors link to various intracellular signaling cascades, which potentially influence different ion channels in a specific and coordinated manner.  We use a combination of multiple approaches to reveal signal transduction pathways mediated by neuromodulators.  Specifically, electrophysiological techniques, such as whole-cell patch-clamp recordings in dissociated or cultured neurons and brain slices, are used to characterize the effect of neuromodulators on glutamate/GABA receptor channels and synaptic transmission. Biochemical and pharmacological approaches are used to identify the signaling molecules linking neuromodulators and channels. Molecular and immunocytochemical techniques are used to detect the expression, localization and trafficking of receptors, ion channels and signaling components in neurons. Moreover, animal models for neurological disorders are used to examine how the neuromodulator actions are altered in these pathological conditions. Our studies will provide knowledge on the molecular and cellular mechanisms underlying the regulation of synaptic transmission by neuromodulators, which is important for mental health and diseases.

 

Keywords:

prefrontal cortex; G protein-coupled receptors; stress hormones; NMDA/AMPA receptor channels; GABAA receptor channels; protein kinases and phosphatases; cytoskeleton; trafficking

 

Contact Information:

Email:                            zhenyan@buffalo.edu
Tel:                                (716) 829-3058 (office), (716) 829-3592 (lab)
Fax:                               (716) 829-2699
Lab location:                  Biomedical Research Building (BRB) Rm. 546-550, Rm. 545

Office location:              BRB Rm. 551 

Mailing address:            124 Sherman Hall, Buffalo, NY 14214

 

Recent Selective Peer-Reviewed Publications:  

2012

  • Jiang H, Ren Y, Yuen EY, Zhong P, Ghaedi M, Hu Z, Azabdaftari G,  Nakaso K, Yan Z, Feng J (2012) Parkin controls dopamine utilization in human midbrain dopaminergic neurons. Nature Communications 3:668. [PDF file]

  • Gu Z, Liu W, Wei J, Yan Z (2012) Regulation of NMDA receptors by metabotropic glutamate receptor 7. J. Biol. Chem. (in press) Epub ahead of print (selected as "Papers of the Week") [PDF file]

  • Yuen EY, Li X, Wei J, Horiguchi M, Meltzer HY, Yan Z (2012) The novel antipsychotic drug lurasidone enhances NMDA receptor-mediated synaptic responses. Mol. Pharm. 81:113-9. [PDF file]

2011

2010

  • Yuen EY, Zhong P, Yan Z (2010) Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors. Proc. Natl. Acad. Sci. USA 107:22308-13. [PDF file] [supporting information]

  • Liu W, Yuen EY, Yan Z (2010) The stress hormone corticosterone increases synaptic AMPA receptors via SGK regulation of the GDI-Rab4 complex. J. Biol. Chem. 285:6101-8. [PDF file]  

  • Wei J, Liu W, Yan Z (2010) Regulation of AMPA receptor trafficking and function by glycogen synthase kinase 3. J. Biol. Chem. 285:26369-76. [PDF file]

  • Yuen EY, Liu W, Kafri T, van Praag H, Yan Z (2010) Regulation of AMPA receptor channels and synaptic plasticity by cofilin phosphatase Slingshot in cortical neurons.. J. Physiol. 588:2361-71. [PDF file]  (cover article)

  • Twelvetrees AE, Yuen EY, Arancibia-Carcamo IL, Rostaing P, Lumb MJ, Humbert S, Triller A, Saudou F, Yan Z, Kittler JT (2010) Delivery of GABAARs to synapses is mediated by HAP1-KIF5 and disrupted by mutant huntingtin. Neuron 65:53-65. [PDF file]

  • Hayashi-Takagi A, Takaki M, Graziane NM, Seshadri S, Murdoch H, Dunlop AJ, Makino Y, Seshadri AJ, Ishizuka K, Srivastava DP, Xie Z, Baraban JM, Houslay MD, Tomoda T, Brandon NJ, Kamiya A, Yan Z, Penzes P, Sawa A (2010) Disrupted-in-Schizophrenia-1 (DISC1) regulates spines of the glutamate synapse via Rac1. Nat. Neurosci. 13:327-32. [PDF file]

  • Joiner MA, Lisé MF, Yuen EY, Kam A, Hall DD, Malik ZA, Qian H, Chen Y, Ulrich JD, Burette AC, Weinberg RJ, Law PY, El-Husseini A, Yan Z, Hell JW (2010) Assembly of a b2-adrenergic receptor- GluR1 signaling complex for localized cAMP signaling. EMBO J 29:482-95. [PDF file]

2009

  •  Yuen EY, Liu W, Karatsoreos IN, Feng J, McEwen BS, Yan Z (2009) Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proc. Natl. Acad. Sci. USA 106:14075-9. [PDF file]

  • Mandal M and Yan Z (2009) PIP2 regulation of NMDA receptor channels in cortical neurons. Mol.  Pharm. 76:1349-59. [PDF file]

  • Liu W, Dou F, Feng J, Yan Z (2009) RACK1 is involved in b-amyloid impairment of muscarinic regulation of GABAergic transmission. Neurobiol. Aging (in press). [PDF file]

  • Arancibia-Cárcamo IL, Yuen EY, Muir J, Lumb MJ, Michels G, Smart TG, Yan Z, Kittler JT, Moss SJ (2009) Ubiquitin-dependent targeting of GABAARs for lysosomal degradation regulates the efficacy of neuronal inhibition. Proc. Natl. Acad. Sci. USA 106:17552-7. [PDF file]

  • Saliba RS, Gu Z, Yan Z, Moss SJ (2009) Blocking L-type voltage gated Ca2+ channels with dihydropyridines reduces gamma-aminobutyric acid type A receptor expression and synaptic inhibition. J Biol Chem. 284:32544-50.

  • Huang YH, Lin Y, Mu P, Marie H, Liu W, Yan Z, Sorg BA, Schluter O,  Zukin SR, Dong Y (2009) Exposure to cocaine generates nascent synapses in the nucleus accumbens. Neuron. 63:40-7. [PDF file]

  • Yuen EY, Yan Z (2009) Dopamine D4 receptors regulate AMPAR trafficking and glutamatergic transmission in GABAergic interneurons of prefrontal cortex. J. Neurosci. 29:550-62. [PDF file]

  • Gu Z, Liu W, Yan Z (2009) b-amyloid Impairs AMPA receptor trafficking and function by reducing CaMKII synaptic distribution. J Biol Chem. 284:10639-49. [PDF file]

  • Graziane NM, Yuen EY, Yan Z (2009) Dopamine D4 receptors regulate GABAA receptor trafficking via an actin/cofilin/myosin-dependent mechanism. J Biol Chem. 284:8329-36. [PDF file]

2008

  • Yuen EY, Jiang Q, Chen P, Feng J, Yan Z (2008) Activation of 5-HT2A/C receptors counteracts 5-HT1A regulation of NMDAR channels in pyramidal neurons of prefrontal cortex. J. Biol. Chem. 283:17194-204.  [PDF file]

  • Zhong P, Liu W, Gu Z, Yan Z (2008) Serotonin facilitates LTD induction in prefrontal cortex via p38 MAPK/Rab5-mediated enhancement of AMPA receptor internalization. J. Physiol. 586:4465-79. [PDF file]

  • Yuen EY, Ren Y, Yan Z (2008) PSD-95 and calcineurin control the sensitivity of NMDA receptors to calpain cleavage in cortical neurons. Mol. Pharmacol. 74:360-370.[PDF file]

  • Zhong P, Yuen EY, Yan Z (2008) Modulation of neuronal excitability by serotonin-NMDA interactions in prefrontal cortex. Mol. and Cell. Neurosci. 38:290-9. [PDF file]

  • Kittler JT, Chen G, Kukhtina V, Vahedi-Faridi A, Gu Z, Tretter V, Smith KR, McAinsh K, Arancibia-Carcamo IL, Saenger W, Haucke V, Yan Z, Moss SJ (2008) Regulation of synaptic inhibition by phospho-dependent binding of the AP2 complex to a YECL motif in the GABAA receptor g2 subunit. Proc Natl Acad Sci. USA 105:3616-21. [PDF file]

  • Chen G, Chen P, Tan H, Ma D, Dou F, Feng J, Yan Z (2008) Regulation of the NMDA receptor-mediated synaptic response by acetylcholinesterase inhibitors and its impairment in an animal model of Alzheimer’s disease. Neurobiol. Aging 29:1795-804. [PDF file]

2007

  • Chen P, Gu Z, Liu W, Yan Z (2007) Glycogen synthase kinase 3 regulates NMDA receptor channel trafficking and function in cortical neurons. Mol. Pharm. 72:40-51. [PDF file]

  • Benavides DR, Quinn JJ, Zhong P, Hawasli AH, Kansy JW, DiLeone R, Yan Z, Taylor JR, Bibb JA (2007) Cyclin-dependent protein kinase 5 controls cocaine responses, motivation for reward, and striatal neuron excitability. J. Neurosci. 27:12967-76. [PDF file]

  • Yuen EY, Liu W, Yan Z (2007) The phosphorylation state of GluR1 subunits determines the susceptibility of AMPA receptors to calpain cleavage. J. Biol. Chem. 282:16434-40. [PDF file]

  • Yuen EY, Gu Z, Yan Z (2007) Calpain regulation of AMPA receptor channels in cortical pyramidal neurons. J Physiol. 580:241-54. [PDF file]

  • Gu Z, Jiang Q, Yan Z (2007) RGS4 modulates serotonin signaling in prefrontal cortex and links to serotonin dysfunction in a rat model of schizophrenia. Mol. Pharmacol. 71:1030-9. [PDF file]

  • Kastning K, Kukhtina V, Kittler JT, Chen G, Pechstein A, Enders S, Lee SH, Sheng M, Yan Z, Haucke V (2007) Molecular determinants for the interaction between AMPA receptors and the clathrin adaptor complex AP-2. Proc. Natl. Acad. Sci. USA 104:2991-6. [PDF file]  

2006

  • Liu W, Yuen EY, Allen PB, Feng J, Greengard P, Yan Z (2006) Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin. Proc. Natl. Acad. Sci. USA 103:18338-43. [PDF file]

  • Jiang Q, Yan Z, Feng J (2006) Activation of group III metabotropic glutamate receptors attenuates rotenone toxicity on dopaminergic neurons through a microtubule-dependent mechanism. J. Neurosci. 26:4318-28. [PDF file]

  • Chen G, Kittler JT, Moss SJ, Yan Z (2006) Dopamine D3 receptors regulate GABA(A) receptor function through a phospho-dependent endocytosis mechanism in nucleus accumbens. J. Neurosci. 26:2511-9. [PDF file]

  • Gu Z,  Jiang Q, Yuen EY, Yan Z (2006) Activation of dopamine D4 receptors induces synaptic translocation of CaMKII in cultured prefrontal cortical neurons. Mol. Pharmacol.  69:813-22. [PDF file]

  • Wang X, Gu Z, Zhong P, Chen G, Feng J, Yan Z (2006) Aberrant regulation of NMDAR functions by dopamine D4 receptors in rats after phencyclidine exposure. Mol. and Cell. Neurosci.  31:15-25. [PDF file]

2005

  • Yuen EY, Jiang Q, Chen P, Gu Z, Feng J, Yan Z (2005) Serotonin 5-HT1A receptors regulate NMDA receptor channels through a microtubule-dependent mechanism. J. Neurosci. 25: 5488-501. [PDF file]

  • Kittler JT, Chen G, Honing S, Bogdanov Y, McAinsh K, Arancibia-Carcamo IL, Jovanovic JN, Pangalos MN, Haucke V, Yan Z and Moss SJ (2005) Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission. Proc. Natl. Acad. Sci. USA 102:14871-6. [PDF file]

  • Gu Z, Jiang Q, Fu AKY, Ip NY, Yan Z (2005) Regulation of NMDA receptors by neuregulin signaling in prefrontal cortex. J. Neurosci. 25: 4974-84. [PDF file]

  • Yuen EY, Jiang Q, Feng J, Yan Z (2005) Microtubule regulation of NMDA receptor channels in neurons. J. Biol. Chem. 280:29420-7. [PDF file]

  • Wu HY*, Yuen EY*, Lu YF, Matsushita M, Matsui H, Yan Z, Tomizawa K (2005) Regulation of NMDA receptors by calpain in cortical neurons. J. Biol. Chem. 280: 21588-93. * co-first author. [PDF file]

  • Tyszkiewicz JP, Yan Z (2005) b-Amyloid peptides impair PKC-dependent functions of metabotropic glutamate receptors in prefrontal cortical neurons. J. Neurophysiol. 93: 3102-11. [PDF file]

 

 

Publication List        Lab Members         Biographical Information        News Release

 

 

Last updated: 1/2012