The brain contains billions of nerve cells, or neurons, which receive and integrate signals from the environment, and which govern the body's responses. Nervous system activity is made possible by synapses, contacts formed either between neurons or between a neuron and a target cell. Synapses are asymmetric structures in which neurotransmitter molecules are released from the presynaptic membrane and activate receptors on the postsynaptic membrane, thus establishing neuronal communication. As such, synapses are fundamental units of neural circuitry and enable complex behaviors.
Research in our lab has focused on mechanisms of synapse formation, neurotransmission, and synaptic plasticity. Our studies contribute to a better understanding of these processes and development of potential therapeutic strategies for psychiatric disorders such as schizophrenia, autism, and depression and neurological disorders such as muscular dystrophy, spinal cord injury, and epilepsy.
Director, Cleveland Brain Health Initiative
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Selected Recent Publications
Z. Dong*, W. Chen*, C. Chen, H. Wang, W. Cui, Z. Tan, H. Robinson, N. Gao, B. Luo, L. Zhang, K. Zhao, W.C. Xiong and L. Mei. CUL3 Deficiency Causes Social Deficits and Anxiety-like Behaviors by Impairing Excitation-Inhibition Balance through the Promotion of Cap-Dependent Translation. Neuron 105: 475-490, 2020 (Cover; Preview by Chen & Maher, Neuron, 105:398-399, 2020).
H. Zhang, W. Chen, Z. Tan, L. Zhang, Z. Dong, W. Cui, K. Zhao, H. Wang, H. Jing, R. Cao, C. Kim, J.G. Safar, W.-C. Xiong and L. Mei. A role of low-density lipoprotein receptor-related protein 4 (LRP4) in astrocytic Aβ clearance. J. Neurosci., 40:5347:5361, 2020
N. Gao, K. Zhao, Y. Cao, X. Ren, H. Jing, G. Xing, W.-C. Xiong, and Lin Mei. A role of lamin A/C in preventing neuromuscular junction decline in mice. J. Neurosci. 40:7203-7215, 2020 (Cover)
M.H. Rivner, B.M. Quarles, J.-X. Pan, Z. Yu, J.F. Howard Jr, A. Corse, M.M. Dimachkie, C. Jackson, T. Vu, G. Small, R.P. Lisak, J. Belsh, I. Lee, R.J. Nowak, V. Baute, S. Scelsa, J.A. Fernandes, Z. Simmons, A. Swenson, R. Barohn, R.B. Sanka, C. Gooch, E. Ubogu, J. Caress, M. Pasnoor, H. Xu, L. Mei. Clinical features of LRP4/agrin-antibody – positive myasthenia gravis: A multicenter study. Muscle & Nerve 62:333–343, 2020.
L. Zhang, H. Jing, H. Li, W. Chen, B. Luo, H-S. Zhang, Z-Q. Dong, L. Li, H-B. Su, W-C. Xiong and L. Mei. Neddylation is critical to cortical development by regulating Wnt/b-catenin signaling. Proc. Nat. Acad. Sci. USA. 117:26448-26459, 2020
G. Xing, H. Jing, L. Zhang, Y. Cao, L. Li, K. Zhao, Z. Dong, W. Chen, H. Wang, R. Cao, W.C. Xiong, and L. Mei. A mechanism in agrin signaling revealed by a prevalent rapsyn mutation in congenital myasthenic syndrome. eLife 8:e49180, 2019
H. Zhang, A. Sathyamurthy, F. Liu, L. Li, L. Zhang, Z. Dong, W. Cui, X. Sun, K. Zhao, H. Wang, H.-Y. H. Ho, W.C. Xiong, L. Mei. Agrin-Lrp4-Ror2 signaling regulates adult hippocampal neurogenesis in mice. eLife 8:e45303, 2019
H. Wang,* F. Liu,* W. Chen,* X. Sun, W. Cui, Z. Dong, K. Zhao, H. Zhang, H. Li, G. Xing, E. Fei, B.-X. Pan, B.-M. Li, W.-C. Xiong, Lin Mei. Genetic recovery of ErbB4 in adulthood partially restores brain functions in null mice. PNAS 115:13105-13110, 2018
K. Zhao*, C. Shen,*,** L. Li, H. Wu, G. Xing, Z. Dong, W. Chen, H. Zhang, J. Pan, H. Wang, W. Cui, X.D. Sun, S. Li, X. Li, X. Huang, W.C. Xiong, and L. Mei**. Sarcoglycan Alpha Mitigation of Neuromuscular Junction Decline in Aged Mice by Stabilizing Lrp4. J. Neurosci. (Front Cover Work, 38 (41) 8860-8873, 2018) *, equal contributing; **, co-corresponding.
X.-D. Sun*,**, W.-B. Chen**, D. Sun**, J. Huang, Y.-Q. Li, J.-X. Pan, Y.-N. Wang, K. Zhao, Z.-Q. Dong, H.-S. Wang, L. Xiong, A. Xuan, S.-T. Zhao, A. Pillai, W.-C. Xiong* and L. Mei. Neogenin in amygdala for neuronal activity and fear memory. J. Neuroscience. J. Neurosci. 38 (44) 9600-9613. (*, co-corresponding; **, co-first)
C. Shen*,**, L. Li**, K. Zhao**, L. Bai, A. Wang, X. Shu, Y. Xiao, J. Zhang, K. Zhang, T. Hui, W. Chen, B. Zhang, W. Hsu, W.-C. Xiong, L. Mei*. Motoneuron Wnts regulate neuromuscular junction development. eLife. 7, 2018 (*, co-corresponding; **, co-first)
Y.-N. Wang, D. Figueiredo, X.-D. Sun, Z.-Q. Dong, W.-B. Chen, W.-P. Cui, F. Liu, H.-S. Wang, H.-W. Li, H. Robinson, E.-K. Fei, B.-X. Pan, B-M Li, W-C Xiong and L. Mei. Controlling of glutamate release by neuregulin3 via inhibiting the assembly of SNARE-complex. Proc. Nat. Acad. Sci. 115:2508-2513, 2018.
T.W. Lin, Z. Tan, A. Barik, D. Yin, E. Brudvik, H. Wang, W.C. Xiong, L. Mei. Regulation of Synapse Development by Vgat Deletion from ErbB4-Positive Interneurons. J. Neurosci. 38:2533-2550, 2018.
M. Yan, Z. Liu, E. Fei, W. Chen, X. Lai, B. Luo, P. Chen, H. Jing, J. Pan, M. Rinver, W.C. Xiong, and L. Mei. Induction of anti-agrin antibodies causes myasthenia gravis in mice. Neuroscience, 373:113-121, 2018.
Z. Tan, H. Robinson, D. Yin, Y. Liu, F. Liu, H. Wang, T.W. Lin, G. Xing, W.C. Xiong, L. Mei. Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents. Neuron, 98:380-393, 2018.
H.F. Jiao*, X.D. Sun*, R. Bates*, L. Xiong, F. Liu, L. Li, H.S. Zhang, S.Q. Wang, M.T. Xiong, M. Patel, A.M. Stranahan, W.C. Xiong, B.M. Li#, L. Mei#. Transmembrane protein 108 is required for glutamatergic transmission in dentate gyrus. Proc. Nat. Acad. Sci. USA. 114: 1177-1182, 2017
(*, equal contributing; #, equal corresponding).
K. Zhao, C. Shen, Y. Lu, Z. Huang, L. Li, C.D. Rand, J. Pan, X.D. Sun, Z. Tan, H. Wang, G. Xing, Y. Cao, W.C. Xiong, and L. Mei. Muscle Yap is a regulator of neuromuscular junction formation and regeneration. J. Neuroscience 37:3465-3477, 2017 (Cover). (Highlighted by Faculty 1000, DOI: 10.3410/f.727317699.793531488).
Li,* Y. Cao,* H. Wu, X. Ye, Z. Zhu, G. Xing, C. Shen, A. Barik, B. Zhang, X. Xie, W. Zhi, L. Gan, H. Su, W.C. Xiong, L. Mei. Enzymatic activity of the scaffold protein rapsyn for synapse formation. Neuron. 2016 Dec 7;92(5):1007-1019. Epub 2016 Nov 10. (*, equal contributing).
H. Wu*, A. Barik*, Y. Lu, C. Shen, A. Bowman, L. Li, A. Sathyamurthy, T.W. Lin, W.C. Xiong, and L. Mei. Slit2 as a β-catenin/Ctnnb1-dependent retrograde signal for presynaptic differentiation. eLife 4:e07266, 2015 (*, co-first).
X.D. Sun,*,** L. Li*, F. Liu, Z.H. Huang, J.C. Bean, H.F. Jiao, A. Barik, S.M. Kim, H. Wu, Shen, Y. Tian, T.W. Lin, R. Bates, A. Sathyamurthy, Y.J. Chen, D.M. Yin, L. Xiong, H.P. Lin, J.X. Hu, B.M. Li, T.M. Gao, W.C. Xiong, Lin Mei**. Lrp4 in astrocytes modulates glutamatergic transmission. Nature Neuroscience 19:1010-1018, 2016 (*, equal contributing; **, corresponding).
A. Barik, L. Li, A. Sathyamurthy, W.-C. Xiong and L. Mei. Schwann Cells in Neuromuscular Junction Formation and Maintenance. J. Neurosci., 36:9770-9781, 2016 (Cover)
Lu,* X.-D. Sun,* F.-Q. Hou, F. Liu, L.L. Bi, D.M. Yin, Y.J. Chen, J. Bean, H.F. Jiao, X. Liu, B.M. Li, W.C. Xiong, T.M. Gao** and L. Mei**. Maintenance of GABAergic activity by neuregulin 1/ErbB4 in amygdala for fear conditioning memory. Neuron 84:835-846, 2014. (*, co-first; **, co-correspondent).
A. Barik, Y. Lu, A. Sathyamurthy, A. Bowman, C. Shen, L. Li, W.-C. Xiong and L. Mei. LRP4 Is Critical for Neuromuscular Junction Maintenance. J.Neurosci. 34:13892-13905, 2014 (Cover)
C. Shen*, B. Zhang*, Y. Lu*, D. Figueiredo, H. Wu, B. Arnab, W.C. Xiong and L. Mei. Antibodies against low-density lipoprotein receptor-related protein 4 induce myasthenia gravis. J. Clin. Invest. 123:5190–5202, 2013.
D.M. Yin*, Y.J. Chen*, Y.S. Lu, J.C. Bean, A. Sathyamurthy, C.Y. Shen, X.H. Liu, T.W. Lin, C.A. Smith, W.C. Xiong, and L. Mei. Reversal of behavioral deficits and synaptic dysfunction in mice overexpressing neuregulin 1. Neuron 78:644-657, 2013.
(Highlighted by Preview, Neuron 78:577, 2013) PMID: 23719163.
Y. Tao*, Y. Chen*, C. Shen*, Z. Luo, C.R. Bates, D. Lee, S. Marchetto, T.-M. Gao, J.-P. Borg, W.C. Xiong, Lin Mei. Erbin interacts with TARP gamma-2 for surface expression of AMPA receptors in cortical interneurons. Nature Neurosci. 16:290-299, 2013. (*, cofirst).
H.T. Wu, Y.S. Lu, C.Y. Shen, W.C. Xiong, L. Mei. Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation. Neuron, 75:94-107, 2012.
Y. Zong, B. Zhang, S. Gu, K. Lee, J. Zhou, G. Yao, D. Figueiredo, K. Perry, L. Mei* and Rongsheng Jin*. Structural basis of agrin–LRP4–MuSK signaling. Genes & Development. 26:247-258, 2012 (Cover) (*, co-correspondence).
B. Zhang, J.S. Tzartos, M. Belimezi, S. Ragheb, B. Bealmear, R.A. Lewis, W.C. Xiong, R.P. Lisak, S.J. Tzartos, Lin Mei. Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Archive Neurol. 69:445-451, 2012. (Highlighted by Editorial, same issue, Archive Neurol., 2012).
S. Luo, B. Zhang, X.-p. Dong, Y. Tao, A. Ting, Z. Zhou, J. Meixiong, J. Luo, F.C.A. Chiu, W.C. Xiong, L. Mei. HSP90β Regulates Rapsyn Turnover and Subsequent AChR Cluster Formation and Maintenance. Neuron 60:97-110, 2008.
(Highlighted at Faculty 1000, DOI: 10.3410/f.1141890.598995)
L. Wen1, Y.S. Lu1, X. Zhu1, X.M. Li, R.-S. Woo, Y.-J. Chen, D.-M. Yin, C. Lai, A. Vazdarjanova, W.C. Xiong, and L. Mei. Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons. Proc. Nat. Acad. Sci. USA 107:1211- 1216, 2010..
B. Zhang, S. Luo, Q. Wang, T. Suzuki, W.C. Xiong, Lin Mei. LRP4 serves as a coreceptor of agrin. Neuron 60:285-297, 2008 (highlighted in Nature 455:1153, 2008; Nature Rev. Neurosci. 9:886, 2008; Neuron, 60:526, 2008).
R.-S. Woo*, X.M. Li*, Y. Tao, E. Carpenter-Hyland, Y.Z. Huang, J. Weber, H. Neiswender, X..-p. Dong, J. Wu, M. Gassmann, C. Lai, W.-C. Xiong, T.-M. Gao1, L. Mei1. Neuregulin-1 Enhances Depolarization-Induced GABA Release. Neuron 54:599-610, 2007 (Highlighted in Neuron 54:495-497, 2007; Nature 448:263, 2007 and Nature Rev. Neurosci., 8:492, 2007). (*, co-contributing; 1, co-correspondence).
Selected Recent Reviews
G. Xing, W.C. Xiong, L. Mei. Rapsyn as a signaling and scaffolding molecule in NMJ formation and maintenance. Neurosci. Lett. 731:1350132, 2020
M Yan, GL Xing, WC Xiong, L Mei. Agrin and LRP4 antibodies as new biomarkers of myasthenia gravis. Ann. New York Acad. Sci. 1413: 126-135, 2018.
L. Li, W.C. Xiong, L. Mei, Neuromuscular junction formation, aging, and disorders. Ann. Rev. Physiol. 2018
Mei and K.-A. Nave, A neuregulin and ErbB network in the nervous system. Neuron 83:27-49, 2014
Wu, Wen C. Xiong, L. Mei. To build a synapse: Signaling pathways in neuromuscular junction assembly. Development 137:1017-1033, 2010
Mei and W.C. Xiong, Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nature Rev. Neurosci. 9:437-452, 2008.