Neurotransmitter release

About

Over the last few decades, one of most important objectives in the field of neuroscience has been to understand the molecular and cellular mechanisms that regulate neurotransmitter release, which drives neuronal communication in the nervous system. Many model organisms have been used to address this question, including the mouse, fly, zebrafish, and octopus. Among these organisms, C. elegans has emerged as a powerful genetic model to study synaptic function. C. elegans, through the study of its functional role in neurotransmission, provides a cost-effective strategy for genetic testing. The Hu group focusses on candidate genes to understand their functional importance in synapses.

Combining electrophysiological recording, cellular imaging, molecular biology, and biochemistry approaches, the Hu group focusses on: 

1. Kinetic regulation of synaptic vesicle release: Understanding the kinetics of how neurotransmitters are released has broad implications. The speed of the neurotransmission limits the efficiency and the communication rate between neurons and strongly influences local circuit dynamics. It has also had profound effects on circuit development and cognition. The Hu laboratory studies synaptic proteins that affect release kinetics to determine the underlying molecular mechanisms.

2. The molecular/cellular mechanisms of different release forms: Neurotransmitters can be released in two forms: evoked fusion after an action potential, and spontaneous fusion. The Hu group focusses on determining the cellular mechanisms underpinning these two release forms. Increasing evidence indicates that different fusion machinery is used for the two forms. Although its physiological function is still uncertain, spontaneous release has been proposed to be important in multiple processes, including long-term facilitation induction and homeostatic synaptic plasticity modulation. 

3. Synaptic transmission defects in neurological diseases: Recent advances in genomic and bioinformatics technologies have identified DNA variants associated with neurological disorders such as autism and motor neuron disease. The Hu lab seeks to understand the functional roles of these candidate genes. 

Contact

  +61 7 334 66395

  z.hu1@uq.edu.au


Group Publications

Research Areas

  • Molecular mechanism of synaptic transmission and synaptic plasticity
  • Release probability at excitatory and inhibitory synapses
  • Synaptic mechanisms for neuropsychiatric disorders. 
  • Function of the neural circuit in regulating behaviour and cognition


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Group Leader

  • Dr ZHITAO Hu

    Senior Research Fellow
    Clem Jones Centre for Ageing Dementia Research

Research Members

  • Haowen Liu

    Mr Haowen Liu

    Postdoctoral Research Fellow
    Clem Jones Centre for Ageing Dementia Research
  • Ray (Lei) Li

    Dr Lei Li

    Postdoctoral Research Fellow
    Clem Jones Centre for Ageing Dementia Research
  • Ms Jing Tang

    Casual Research Assistant
    Queensland Brain Institute

Students

Haowen Liu, Lei Li, Daniel Nedelcu, Qi Hall, Lijun Zhou, Wei Wang, Yi Yu, Joshua M. Kaplan, Zhitao Hu. (2019) Heterodimerization of UNC-13/RIM regulates synaptic vesicle release probability but not priming. eLife. In press.

Vina Tikiyani, Lei Li, Pallavi Sharma, Haowen Liu, Zhitao Hu and Kavita Babu. (2018). Wnt secretion is regulated by the claudin-like protein, HIC-1, through its interaction with Neurabin/NAB-1. Cell Reports, 25, 1856-1871

Sharma, P.#, Li, L.#, Liu, H., Tikiyani, V., Hu, Z.*, and Babu, K.* (2018). The Claudin-like protein HPO-30 is required to maintain LAChRs at the C. elegans neuromuscular junction. The Journal of Neuroscience. June 27. 3487-17 (*, Corresponding authors)

Li, L., Liu, H., Wang, W., Chandra, M., Collins, B., and Hu, Z. (2018). SNT-1 functions as the Ca2+ sensor for spontaneous and evoked neurotransmitter release in C. elegans. The Journal of Neuroscience. June 6, 38(23):5313–5324

Liu, H., Li, L., Wang W., Gong, J., Yang, X., and Hu, Z. (2018). Spontaneous vesicle fusion is differentially regulated at cholinergic and GABAergic synapses of the C. elegans neuromuscular junction. Cell Reports, 22, 1-12.

Gao S.B., Hu, Z. (2018). In vivo recordings at Caenorhabditis elegans neuromuscular junction. Springer Nature. Extracellular Recording Approaches, Neuromethods, vol. 134

Michelassi F., Liu H.W., Hu Z., and Dittman J. (2017). A novel synaptic inhibitory function for the Munc13 C1-C2B module controls calcium-dependent neurotransmitter release. Neuron, 95, 577-590.

Tong, X.J., Soto J.L., Li L., Liu H.W., Nedelcul D., Lipscombe D., Hu, Z., and Kaplan, J.M. (2017). Retrograde synaptic inhibition is mediated by a-Neurexin binding to the α2δ subunits of N-type calcium channels. Neuron 95, 326-340.

Du, H., Zhang, M., Yao, K., and Hu, Z. (2017). Protective effect of Aster tataricus extract on retinal damage on the virtue of its antioxidant and anti-inflammatory effect in diabetic rat. Biomed Pharmacother 89, 617-622.

Tong, X.J.*, Hu, Z.*, Liu, Y., Anderson, D., and Kaplan, J.M. (2015). A network of autism linked genes stabilizes two pools of synaptic GABAA receptors. Elife 4. (*, co-first author)

Hu, Z., Vashlishan-Murray, A.B., and Kaplan, J.M. (2015). NLP-12 engages different UNC-13 proteins to potentiate tonic and evoked release. Journal of Neuroscience 35, 1038-1042.

Choi, S., Taylor, K.P., Chatzigeorgiou, M., Hu, Z., Schafer, W.R., and Kaplan, J.M. (2015). Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release. PLoS Genet 11, e1005359.

Sun, Y., Hu, Z., Goeb, Y., and Dreier, L. (2013). The F-box protein MEC-15 (FBXW9) promotes synaptic transmission in GABAergic motor neurons in C. elegans. PLoS One 8, e59132.

Hu, Z., Tong, X.J., and Kaplan, J.M. (2013). UNC-13L, UNC-13S, and Tomosyn form a protein code for fast and slow neurotransmitter release in Caenorhabditis elegans. Elife 2, e00967.

Thompson-Peer, K.L., Bai, J., Hu, Z., and Kaplan, J.M. (2012). HBL-1 patterns synaptic remodeling in C. elegans. Neuron 73, 453-465.

Hu, Z., Hom, S., Kudze, T., Tong, X.J., Choi, S., Aramuni, G., Zhang, W., and Kaplan, J.M. (2012). Neurexin and neuroligin mediate retrograde synaptic inhibition in C. elegans. Science 337, 980-984.

Hao, Y., Hu, Z., Sieburth, D., and Kaplan, J.M. (2012). RIC-7 promotes neuropeptide secretion. PLoS Genet 8, e1002464.

Chan, J.P., Hu, Z., and Sieburth, D. (2012). Recruitment of sphingosine kinase to presynaptic terminals by a conserved muscarinic signaling pathway promotes neurotransmitter release. Genes Dev 26, 1070-1085.

Martin, J.A.*, Hu, Z.*, Fenz, K.M., Fernandez, J., and Dittman, J.S. (2011). Complexin has opposite effects on two modes of synaptic vesicle fusion. Curr Biol 21, 97-105. (*, co-first author)

Hu, Z., Pym, E.C., Babu, K., Vashlishan Murray, A.B., and Kaplan, J.M. (2011). A neuropeptide-mediated stretch response links muscle contraction to changes in neurotransmitter release. Neuron 71, 92-102.

Babu, K., Hu, Z., Chien, S.C., Garriga, G., and Kaplan, J.M. (2011). The immunoglobulin super family protein RIG-3 prevents synaptic potentiation and regulates Wnt signaling. Neuron 71, 103-116.

Bai, J., Hu, Z., Dittman, J.S., Pym, E.C., and Kaplan, J.M. (2010). Endophilin functions as a membrane-bending molecule and is delivered to endocytic zones by exocytosis. Cell 143, 430-441.

Hu, Z.T., Chen, M.R., Ping, Z., Dong, Y.M., Zhang, R.Y., Xu, T., and Wu, Z.X. (2008). Synaptotagmin IV regulates dense core vesicle (DCV) release in LbetaT2 cells. Biochem Biophys Res Commun 371, 781-786.

Hu, Z., Dun, X., Zhang, M., Zhu, H., Xie, L., Wu, Z., Chen, Z., and Xu, T. (2007). PA1b, a plant peptide, induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel and triggers secretion in pancreatic beta cells. Sci China C Life Sci 50, 285-291.

Liu, H.S.*, Hu, Z.T.*, Zhou, K.M., Jiu, Y.M., Yang, H., Wu, Z.X., and Xu, T. (2006). Heterogeneity of the Ca2+ sensitivity of secretion in a pituitary gonadotrope cell line and its modulation by protein kinase C and Ca2+. J Cell Physiol 207, 668-674. (*, co-first author)

Hu, Z.T., Zhao, P., Liu, J., Wu, Z.X., and Xu, T. (2006). Alpha-latrotoxin triggers extracellular Ca2+-dependent exocytosis and sensitizes fusion machinery in endocrine cells. Acta Biochim Biophys Sin (Shanghai) 38, 8-14.

Ge, Q., Dong, Y.M., Hu, Z.T., Wu, Z.X., and Xu, T. (2006). Characteristics of Ca2+-exocytosis coupling in isolated mouse pancreatic beta cells. Acta Pharmacol Sin 27, 933-938.

Yang, H., Liu, H., Hu, Z., Zhu, H., and Xu, T. (2005). PKC-induced sensitization of Ca2+-dependent exocytosis is mediated by reducing the Ca2+ cooperativity in pituitary gonadotropes. J Gen Physiol 125, 327-334.

Paper Under Review or In Revision:

Lei Li, Haowen Liu, Qi Hall, Wei Wang, Josh Kaplan, Zhitao Hu. A hyper-active form of unc-13 enhances Ca2+ sensitivity and synaptic vesicle release probability in C. elegans. (2019) Cell Reports. In revision.

Investigation of the function of the scaffolding protein LIN-2/CASK in cholinergic synapses
(2017–2020) NHMRC Project Grant

Investigating the Molecular Mechanism of Synaptic Transmission
(2016–2019) ARC Discovery Projects

Investigating the timing of neurotransmission
(2018) UQ Foundation Research Excellence Awards - DVC(R) Funding

To investigate the presynaptic mechanism of neurotransmission
(2016–2017) UQ Early Career Researcher

NARSAD Young Investigator Grant, NARSAD                                                   
(2017 – 2019)

BRAIN Initiative R21 (1R21EY029450-01), NIH/NEI                                   
(2019 – 2021)


  • Professor Josh Kaplan - Harvard University, Boston, USA
  • Professor Tao Xu – Chinese Academy of Sciences, Institute of Biophysics, Beijing, China
  • Associate Professor Jeremy Dittman - Cornell University, New York, USA
  • Assistant Professor Kavita Babu - Indian Institute of Science Education & Research (IISER), Mohali
  • Professor Zhiqi Xiong - Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China