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Research Highlight

ZHANG lab's research mainly focuses on mechanistic basis of synapse formation and plasticity. We recently discovered that both postsynaptic densities at excitatory and inhibitory synapses and presynaptic active zones are formed via liquid-liquid phase separation (LLPS). We strive to understand implications of LLPS-mediated synapse formation in neuronal functions. We are also actively working on why mutations of genes encoding synaptic proteins can cause various neuronal diseases including psychiatric disorders and neurodegenerative diseases. Our studies of phase separation in neuronal synapses also shed light on functions of membraneless organelles in cells in general.

Both excitatory and inhibitory postsynaptic densities are formed via phase separation.

Presynaptic bouton organizationis governed by phase separation.

Phase separation has general implications in cell biology.

Molecular basis underling DISC 1-mediated neurogenesis.

Research

Neuronal Structural Biology

Biochemical and structural basis of important biomacromolecular complexes in nerve signal transduction.

Synaptic Molecular Biology

Molecular mechanisms of synaptic generation, maturation, and plasticity

Phase Separation In Nervous System

Molecular mechanism of the occurrence and regulation of phase transition and phase separation of biomacromolecules.

Selected PUBLICATIONS

Demixing is a default process for biological condensates formed via phase separation

Zhu, S., Shen, Z., Wu, X., Han, W., Jia, B., Lu, W., & Zhang, M. (2024). Science, 384(6698), 920-928.
Short-distance vesicle transport via phase separation.

Qiu, H., Wu, X., Ma, X., Li, S., Cai, Q., Ganzella, M., ... & Zhang, M. (2024). Cell.
Vesicle tethering on the surface of phase-separated active zone condensates

Wu, X., Ganzella, M., Zhou, J., Zhu, S., Jahn, R., & Zhang, M. (2021). Molecular Cell, 81(1), 13-24.
CaMKIIα-driven, phosphatase-checked postsynaptic plasticity via phase separation

Cai, Q., Zeng, M., Wu, X., Wu, H., Zhan, Y., Tian, R., & Zhang, M. (2021). Cell Research, 31(1), 37-51.

ALL PUBLICATIONS

2024
2023
2022
2021
2020
2019
2018
2017
2016
2015
2014
2013
2012
2011
Before 2010

AIDA-1/ANKS1B Binds to the SynGAP Family RasGAPs with High Affinity and Specificity.

Wang, X., Wang, Y., Cai, Q., & Zhang, M. (2024). Journal of Molecular Biology, 436(12), 168608.
Demixing is a default process for biological condensates formed via phase separation

Zhu, S., Shen, Z., Wu, X., Han, W., Jia, B., Lu, W., & Zhang, M. (2024). Science, 384(6698), 920-928.
Short-distance vesicle transport via phase separation.

Qiu, H., Wu, X., Ma, X., Li, S., Cai, Q., Ganzella, M., ... & Zhang, M. (2024). Cell.
Phosphorylation-dependent membraneless organelle fusion and fission illustrated by postsynaptic density assemblies.

Wu, H., Chen, X., Shen, Z., Li, H., Liang, S., Lu, Y., & Zhang, M. (2024). Molecular Cell, 84(2), 309-326.

Ca²⁺-induced release of IQSEC2/BRAG1 autoinhibition under physiological and pathological conditions

Bai, G., Li, H., Qin, P., Guo, Y., Yang, W., Lian, Y., ... & Zhang, M. (2023). Journal of Cell Biology, 222(12).
Phase separation-mediated actin bundling by the postsynaptic density condensates

Chen X, Jia B, Zhu S, Zhang, M. [J]. Elife, 2023, 12: e84446.
Biological condensates form percolated networks with molecular motion properties distinctly different from dilute solutions

Shen Z, Jia B, Xu Y, ...Zhang, M, et al. [J]. Elife, 2023, 12: e81907.
Differential roles of CaMKII isoforms in phase separation with NMDA receptors and in synaptic plasticity

Cai Q, Chen X, Zhu S, ... & Zhang, M.[J]. Cell Reports, 2023, 42(3).
Structural and mechanistic insights into fungal β-1, 3-glucan synthase FKS1.

Hu X, Yang P, Chai C, Zhang M, et al. [J]. Nature, 2023: 1-9.

Long-term potentiation reconstituted with an artificial TARP/PSD-95 complex

Ravi, A. S., Zeng, M., Chen, X., Sandoval, G., Diaz-Alonso, J., Zhang, M., & Nicoll, R. A. (2022). Cell reports, 41(2), 111483.
Arc weakens synapses by dispersing AMPA receptors from postsynaptic density via modulating PSD phase separation

Chen, X., Jia, B., Araki, Y., Liu, B., Ye, F., Huganir, R., & Zhang, M. (2022). Cell Research, 32(10), 914-930.
IRSp53 promotes postsynaptic density formation and actin filament bundling

Feng, Z., Lee, S., Jia, B., Jian, T., Kim, E., & Zhang, M. (2022).Journal of Cell Biology, 221(8), e202105035.
O-GlcNAcylation modulates liquid–liquid phase separation of SynGAP/PSD-95

Lv, P., Du, Y., He, C., Peng, L., Zhou, X., Wan, Y., Zhang, M., ... & Chen, X. (2022).
Inhibitory postsynaptic density from the lens of phase separation

Bai, G., & Zhang, M. (2022). Oxford Open Neuroscience, 1

Site-specific phosphorylation of PSD-95 dynamically regulates the postsynaptic density as observed by phase separation

Vistrup-Parry, M., Chen, X., Johansen, T.L., Bach, S., Buch-Larsen, S.C., Bartling, C.R.O., Ma, C., Clemmensen, L.S., Nielsen, M.L., Zhang, M, and Strømgaard, K. (2021) iScience 24, 103268.
Phase Separation of MAGI2-Mediated Complex Underlies Formation of Slit Diaphragm Complex in Glomerular Filtration Barrier

Zhang, H., Lin, L., Liu, J., Pan, L., Lin, Z., Zhang, M., ... & Zhang, R. (2021). Journal of the American Society of Nephrology, 32(8), 1946-1960.
Presynaptic bouton compartmentalization and postsynaptic density-mediated glutamate receptor clustering via phase separation

Feng, Z., Wu, X., & Zhang, M. (2021). Neuropharmacology, 193, 108622.
Liquid–liquid phase separation in biology: specific stoichiometric molecular interactions vs promiscuous interactions mediated by disordered sequences

Feng, Z., Jia, B., & Zhang, M. (2021). Biochemistry, 60(31), 2397-2406.
Entropy of stapled peptide inhibitors in free state is the major contributor to the improvement of binding affinity with the GK domain

Unarta, I. C., Xu, J., Shang, Y., Cheung, C. H. P., Zhu, R., Chen, X., Zhang, M., ... & Li, X. (2021).RSC Chemical Biology, 2(4), 1274-1284.

Liquid-liquid phase separation in neuronal development and synaptic signaling

Wu, X., Cai, Q., Feng, Z., & Zhang, M. (2020). Developmental cell, 55(1), 18-29.
A WW tandem-mediated dimerization mode of SAV1 essential for Hippo signaling

Lin, Z., Xie, R., Guan, K., & Zhang, M. (2020). Cell reports, 32(10), 108118.
GIT/PIX condensates are modular and ideal for distinct compartmentalized cell signaling

Zhu, J., Zhou, Q., Xia, Y., Lin, L., Li, J., Peng, M., ... & Zhang, M. (2020). Molecular Cell, 79(5), 782-796.
Giant ankyrin-B suppresses stochastic collateral axon branching through direct interaction with microtubules

Chen, K., Yang, R., Li, Y., Zhou, J. C., & Zhang, M. (2020). Journal of Cell Biology, 219(8).
Structural basis underlying strong interactions between ankyrins and spectrins

Li, J., Chen, K., Zhu, R., & Zhang, M. (2020). Journal of molecular biology, 432(13), 3838-3850.

Phase separation-mediated TARP/MAGUK complex condensation and AMPA receptor synaptic transmission

Zeng, M., Díaz-Alonso, J., Ye, F., Chen, X., Xu, J., Ji, Z., ... & Zhang, M. (2019). Neuron, 104(3), 529-543.
Myosin VII, USH1C, and ANKS4B or USH1G together form condensed molecular assembly via liquid-liquid phase separation

He, Y., Li, J., & Zhang, M. (2019). Cell reports, 29(4), 974-986.
Decoding WW domain tandem-mediated target recognitions in tissue growth and cell polarity

Lin, Z., Yang, Z., Xie, R., Ji, Z., Guan, K., & Zhang, M. (2019). Elife, 8, e49439.
Structure of the MORN4/Myo3a tail complex reveals MORN repeats as protein binding modules

Li, J., Liu, H., Raval, M. H., Wan, J., Yengo, C. M., Liu, W., & Zhang, M. (2019). Structure, 27(9), 1366-1374.
Formation of biological condensates via phase separation: Characteristics, analytical methods, and physiological implications

Feng, Z., Chen, X., Wu, X., & Zhang, M. (2019). Journal of Biological Chemistry, 294(40), 14823-14835.

An unexpected INAD PDZ tandem-mediated plcβ binding in Drosophila photo receptors

Ye, F., Huang, Y., Li, J., Ma, Y., Xie, C., Liu, Z., Deng, X., Wan, J., Xue, T., Liu, W., and Zhang, M.(2018). eLife, 7, e41848.
Ankyrin-G regulates forebrain connectivity and network synchronization via interaction with GABARAP

Nelson, A. D., Caballero-Florán, R. N., Rodríguez Díaz, J. C., Hull, J. M., Yuan, Y., Chen, K., ..., Wang, C., Zhang, M., Jones, K. S., and Jenkins, P. M.,(2018). Molecular Psychiatry, 1.
Protein complex assemblies in epithelial cell polarity and asymmetric cell division

Wen, W., & Zhang, M. (2018). Journal of molecular biology, 430(19), 3504-3520.
Reconstituted Postsynaptic Density as a Molecular Platform for Understanding Synapse Formation and Plasticity

Zeng, M., Chen, X., Guan, D., Xu, J., Wu, H., Tong, P., and Zhang, M.(2018). Cell, 174, 1-16.
Bi-allelic Mutations in Phe-tRNA Synthetase Associated with a Multi-system Pulmonary Disease Support Non-translational Function

Xu, Z., Lo, W., ... and Zhang, M.,..., and Schimmel, P.,(2018) . The American Journal of Human Genetics, 103, 100-114.

Synaptic targeting and function of SAPAPs mediated by phosphorylation-dependent binding to PSD-95 MAGUKs

Zhu, J., Zhou, Q., Shang, Y., Li, H., Peng, M., Ke, X., ... & Zhang, M. (2017). Cell reports, 21(13), 3781-3793.
DISC1 regulates neurogenesis via modulating kinetochore attachment of Ndel1/Nde1 during mitosis

Ye, F., Kang, E., Yu, C., Qian, X., Jacob, F., Yu, C., ... & Zhang, M. (2017). Neuron, 96(5), 1041-1054.
SAP97 binding partner CRIPT promotes dendrite growth in vitro and in vivo

Zhang, L., Jablonski, A. M., Mojsilovic-Petrovic, J., Ding, H., Seeholzer, S., Newton, I. P., Zhang, M., ... & Kalb, R. G. (2017).Eneuro, 4(6).
The structure of the ZMYND8/Drebrin complex suggests a cytoplasmic sequestering mechanism of ZMYND8 by Drebrin

Yao, N., Li, J., Liu, H., Wan, J., Liu, W., & Zhang, M. (2017). Structure, 25(11), 1657-1666.
Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity

Ma, Q., Ruan, H., Peng, L., Zhang, M., Gack, M. U., & Yao, W. D. (2017). Proceedings of the National Academy of Sciences, 114(41), E8760-E8769.

An atypical MAGUK GK target recognition mode revealed by the interaction between DLG and KIF13B

Zhu, J., Shang, Y., Xia, Y., Zhang, R., & Zhang, M. (2016). Structure, 24(11), 1876-1885.
Phase transition in postsynaptic densities underlies formation of synaptic complexes and synaptic plasticity

Zeng, M., Shang, Y., Araki, Y., Guo, T., Huganir, R. L., & Zhang, M. (2016). Cell, 166(5), 1163-1175.
A binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function

Zeng, M., Shang, Y., Guo, T., He, Q., Yung, W. H., Liu, K., & Zhang, M. (2016).Proceedings of the National Academy of Sciences, 113(22), E3081-E3090.
Mechanistic basis of MAGUK-organized complexes in synaptic development and signalling

Zhu, J., Shang, Y., & Zhang, M. (2016). Nature Reviews Neuroscience, 17(4), 209-223.
An exquisitely specific PDZ/target recognition revealed by the structure of INAD PDZ3 in complex with TRP channel tail

Ye, F., Liu, W., Shang, Y., & Zhang, M. (2016). Structure, 24(3), 383-391.

The structural basis of Miranda-mediated Staufen localization during Drosophila neuroblast asymmetric division

Jia, M., Shan, Z., Yang, Y., Liu, C., Li, J., Luo, Z. G., Zhang, M., ... & Wang, W. (2015). Nature communications, 6(1), 8381.
Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic β cell insufficiency

Lorenzo, D. N., Healy, J. A., Hostettler, J., Davis, J., Yang, J., Wang, C., Zhang, M., ... & Bennett, V. (2015). The Journal of clinical investigation, 125(8), 3087-3102.
Site selective Azo coupling for peptide cyclization and affinity labeling of an SH3 protein

Huang, F., Nie, Y., Ye, F., Zhang, M., & Xia, J. (2015). Bioconjugate Chemistry, 26(8), 1613-1622.
Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway

Li, Y., Zhou, H., Li, F., Chan, S. W., Lin, Z., Wei, Z., ... & Zhang, M. (2015). Cell research, 25(7), 801-817.
Unexpected heterodivalent recruitment of NOS1AP to nNOS reveals multiple sites for pharmacological intervention in neuronal disease models

Li, L. L., de Mera, R. M. M. F., Chen, J., Ba, W., Kasri, N. N., Zhang, M., & Courtney, M. J. (2015). Journal of Neuroscience, 35(19), 7349-7364.

Suppression of subtelomeric VSG switching by Trypanosoma brucei TRF requires its TTAGGG repeat-binding activity

Jehi, S. E., Li, X., Sandhu, R., Ye, F., Benmerzouga, I., Zhang, M., ... & Li, B. (2014). Nucleic acids research, 42(20), 12899-12911.
Structure of Crumbs tail in complex with the PALS1 PDZ–SH3–GK tandem reveals a highly specific assembly mechanism for the apical Crumbs complex

Li, Y., Wei, Z., Yan, Y., Wan, Q., Du, Q., & Zhang, M. (2014). Proceedings of the National Academy of Sciences, 111(49), 17444-17449.
Structural basis of diverse membrane target recognitions by ankyrins

Wang, C., Wei, Z., Chen, K., Ye, F., Yu, C., Bennett, V., & Zhang, M. (2014). Elife, 3, e04353.
Cargo recognition and cargo-mediated regulation of unconventional myosins

Lu, Q., Li, J., & Zhang, M. (2014). Accounts of chemical research, 47(10), 3061-3070.
Human tRNA synthetase catalytic nulls with diverse functions

Lo, W. S., Gardiner, E., Xu, Z., Lau, C. F., Wang, F., Zhou, J. J., ... Zhang, M., & Schimmel, P. (2014). Science, 345(6194), 328-332.

Structures and target recognition modes of PDZ domains: recurring themes and emerging pictures

Ye, F., & Zhang, M. (2013). Biochemical Journal, 455(1), 1-14.
Regulated capture by exosomes of mRNAs for cytoplasmic tRNA synthetases

Wang, F., Xu, Z., Zhou, J., Lo, W. S., Lau, C. F., Nangle, L. A., ... Zhang, M., & Schimmel, P. (2013). Journal of Biological Chemistry, 288(41), 29223-29228.
Structural basis of cargo recognitions for class V myosins

Wei, Z., Liu, X., Yu, C., & Zhang, M. (2013). Proceedings of the National Academy of Sciences, 110(28), 11314-11319.
The Par3/Par6/aPKC complex and epithelial cell polarity

Chen, J., & Zhang, M. (2013). Experimental cell research, 319(10), 1357-1364.
Structural insights into the intrinsic self-assembly of Par-3 N-terminal domain

Zhang, Y., Wang, W., Chen, J., Zhang, K., Gao, F., Gao, B., Zhang, M., ... & Feng, W. (2013). Structure, 21(6), 997-1006.

Structure and function of the guanylate kinase-like domain of the MAGUK family scaffold proteins

Zhu, J., Shang, Y., Chen, J., & Zhang, M. (2012). Frontiers in biology, 7, 379-396.
Antiparallel coiled-coil–mediated dimerization of myosin X

Lu, Q., Ye, F., Wei, Z., Wen, Z., & Zhang, M. (2012). Proceedings of the National Academy of Sciences, 109(43), 17388-17393.
The CC1-FHA tandem as a central hub for controlling the dimerization and activation of kinesin-3 KIF1A

Huo, L., Yue, Y., Ren, J., Yu, J., Liu, J., Yu, Y., ... Zhang, M., & Feng, W. (2012). Structure, 20(9), 1550-1561.
Internally deleted human tRNA synthetase suggests evolutionary pressure for repurposing

Xu, Z., Wei, Z., Zhou, J. J., Ye, F., Lo, W. S., Wang, F., ... Zhang, M., & Schimmel, P. (2012). Structure, 20(9), 1470-1477.
Membrane-induced lever arm expansion allows myosin VI to walk with large and variable step sizes

Yu, C., Lou, J., Wu, J., Pan, L., Feng, W., & Zhang, M. (2012). Journal of Biological Chemistry, 287(42), 35021-35035.

Structural basis of the myosin X PH1N-PH2-PH1C tandem as a specific and acute cellular PI (3, 4, 5) P3 sensor

Lu, Q., Yu, J., Yan, J., Wei, Z., & Zhang, M. (2011). Molecular biology of the cell, 22(22), 4268-4278.
The structure of the PDZ3-SH3-GuK tandem of ZO-1 protein suggests a supramodular organization of the membrane-associated guanylate kinase (MAGUK) family scaffold protein core

Pan, L., Chen, J., Yu, J., Yu, H., & Zhang, M. (2011). Journal of Biological Chemistry, 286(46), 40069-40074.
Liprin-mediated large signaling complex organization revealed by the liprin-α/CASK and liprin-α/liprin-β complex structures

Wei, Z., Zheng, S., Spangler, S. A., Yu, C., Hoogenraad, C. C., & Zhang, M. (2011). Molecular cell, 43(4), 586-598.
LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in asymmetric cell division for the Par3/mInsc/LGN and Gαi/LGN/NuMA pathways

Zhu, J., Wen, W., Zheng, Z., Shang, Y., Wei, Z., Xiao, Z., ... & Zhang, M. (2011). Molecular cell, 43(3), 418-431.
The INAD scaffold is a dynamic, redox-regulated modulator of signaling in the Drosophila eye

Liu, W., Wen, W., Wei, Z., Yu, J., Ye, F., Liu, C. H., ... & Zhang, M. (2011). Cell, 145(7), 1088-1101

MEMBERS

Mainly engaged in structural biology,
Biochemistry and
Molecular biology research.

Mingjie ZHANG

Kerry Holdings Professor of Science
Director of Center for Systems Biology and
Human Health
Chair Professor, Division of Life Science
Member of Chinese Academy of Science

2020 Winners
Tan Jiazhen Life Science Award
Elected in 2011
Academician of Chinese Academy of Sciences
2003 Winners
Croucher Foundation Outstanding Scholar Award

Zhang Mingjie | Born in Ningbo, Zhejiang in September 1966

Mainly engaged in structural biology,
biochemistry and
molecular biology research.

· Structural biologist,
· Academician of the Chinese Academy of Sciences,
· Founding Academician of the Hong Kong Academy of Sciences,
· Kerry Science Title Professor, Division of Life Sciences, Hong Kong University of Science and Technology. Dean of the School of Life Sciences, University of Science and Technology of China,
· Dean of the School of Life Sciences, SUSTech.

In 1988 graduated from Fudan University;

In 1993 he obtained a doctorate degree from the University of Calgary, Canada;

In 1995 he joined the Department of Biochemistry, Hong Kong University of Science and Technology, and served as assistant professor, associate professor and professor successively;

In 2003 won the Hong Kong Croucher Foundation Outstanding Scholar Award;

In 2011 he was elected as an academician of the Chinese Academy of Sciences;

In 2015 he was elected as a founding member of the Hong Kong Academy of Sciences.