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

  • Neurotransmitter release mechanisms and neuronal communication 
  • Kinetic regulation of synaptic vesicle release
  • Evoked and spotaneous fusion 
  • Synaptic transmission defects in neurological diseases


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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

Gao S.B., Hu, Z. (2017). In vivo recordings at Caenorhabditis elegans neuromuscular junction. Springer Nature. Accepted.

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, Accepted.

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, Xia-Jing, Hu, Zhitao, Liu, Yu, Anderson, Dorian and Kaplan, Joshua M. (2015) A network of autism linked genes stabilizes two pools of synaptic GABAA receptorseLife4 e09648: . doi:10.7554/eLife.09648

Tong XJ, Hu Z, Liu Y, Anderson D, Kaplan JM. A network of autism linked genes  stabilizes two pools of synaptic GABA(A) receptors. Elife. 2015 Nov 17;4:e09648.  doi: 10.7554/eLife.09648. PubMed PMID: 26575289; PubMed Central PMCID: PMC4642926.

Choi S, Taylor KP, Chatzigeorgiou M, Hu Z, Schafer WR, Kaplan JM. Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release. PLoS Genet. 2015 Jul 8;11(7):e1005359. doi: 10.1371/journal.pgen.1005359. PubMed  PMID: 26154367; PubMed Central PMCID: PMC4495980.

Hu Z, Vashlishan-Murray AB, Kaplan JM. NLP-12 engages different UNC-13 proteins to potentiate tonic and evoked release. J Neurosci. 2015 Jan 21;35(3):1038-42. doi: 10.1523/JNEUROSCI.2825-14.2015. PubMed PMID: 25609620; PubMed Central PMCID: PMC4300317.

Hu Z, Tong XJ, Kaplan JM. UNC-13L, UNC-13S, and Tomosyn form a protein code for fast and slow neurotransmitter release in Caenorhabditis elegans. Elife. 2013 Aug 13;2:e00967. doi: 10.7554/eLife.00967. PubMed PMID: 23951547; PubMed Central  PMCID: PMC3743133.

Sun Y, Hu Z, Goeb Y, Dreier L. The F-box protein MEC-15 (FBXW9) promotes synaptic transmission in GABAergic motor neurons in C. elegans. PLoS One. 2013;8(3):e59132. doi: 10.1371/journal.pone.0059132. PubMed PMID: 23527112; PubMed Central PMCID: PMC3601060.

Hu Z, Hom S, Kudze T, Tong XJ, Choi S, Aramuni G, Zhang W, Kaplan JM. Neurexin and neuroligin mediate retrograde synaptic inhibition in C. elegans. Science. 2012 Aug 24;337(6097):980-4. doi: 10.1126/science.1224896. PubMed PMID: 22859820; PubMed Central PMCID: PMC3791080.

Chan JP, Hu Z, Sieburth D. Recruitment of sphingosine kinase to presynaptic terminals by a conserved muscarinic signaling pathway promotes neurotransmitter release. Genes Dev. 2012 May 15;26(10):1070-85. doi: 10.1101/gad.188003.112. PubMed PMID: 22588719; PubMed Central PMCID: PMC3360562.

Thompson-Peer KL, Bai J, Hu Z, Kaplan JM. HBL-1 patterns synaptic remodeling in C. elegans. Neuron. 2012 Feb 9;73(3):453-65. doi: 10.1016/j.neuron.2011.11.025. PubMed PMID: 22325199; PubMed Central PMCID: PMC3278716.

Hao Y, Hu Z, Sieburth D, Kaplan JM. RIC-7 promotes neuropeptide secretion. PLoS Genet. 2012 Jan;8(1):e1002464. doi: 10.1371/journal.pgen.1002464. PubMed PMID: 22275875; PubMed Central PMCID: PMC3261915.

Babu K, Hu Z, Chien SC, Garriga G, Kaplan JM. The immunoglobulin super family protein RIG-3 prevents synaptic potentiation and regulates Wnt signaling. Neuron. 2011 Jul 14;71(1):103-16. doi: 10.1016/j.neuron.2011.05.034. PubMed PMID: 21745641; PubMed Central PMCID: PMC3134796.

Hu Z, Pym EC, Babu K, Vashlishan Murray AB, Kaplan JM. A neuropeptide-mediated stretch response links muscle contraction to changes in neurotransmitter release. Neuron. 2011 Jul 14;71(1):92-102. doi: 10.1016/j.neuron.2011.04.021. PubMed PMID: 21745640; PubMed Central PMCID: PMC3134788.

Martin JA, Hu Z, Fenz KM, Fernandez J, Dittman JS. Complexin has opposite effects on two modes of synaptic vesicle fusion. Curr Biol. 2011 Jan 25;21(2):97-105. doi: 10.1016/j.cub.2010.12.014. PubMed PMID: 21215634; PubMed Central PMCID: PMC3026084.

Bai J, Hu Z, Dittman JS, Pym EC, Kaplan JM. Endophilin functions as a membrane-bending molecule and is delivered to endocytic zones by exocytosis. Cell. 2010 Oct 29;143(3):430-41. doi: 10.1016/j.cell.2010.09.024. PubMed PMID: 21029864; PubMed Central PMCID: PMC2996235.

Hu Z, Dun X, Zhang M, Zhu H, Xie L, Wu Z, Chen Z, Xu T. 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. 2007 Jun;50(3):285-91. PubMed PMID: 17609883.

Yang H, Liu H, Hu Z, Zhu H, Xu T. PKC-induced sensitization of Ca2+-dependent exocytosis is mediated by reducing the Ca2+ cooperativity in pituitary gonadotropes. J Gen Physiol. 2005 Mar;125(3):327-34. PubMed PMID: 15710914; PubMed Central PMCID: PMC2234013.

 


  • 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