Neurotransmitter release

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. 

Group leader


Associate Professor Zhitao Hu

Senior Research Fellow, Queensland Brain Institute

  +61 7 334 66395
  UQ Researcher Profile

Investigating the coordinated functions of a dual Ca2+ sensor system in C. elegans

(2022 - 2023) NIH/NINDS (R01 NS128048), Janet Richmond, Zhitao Hu.

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)

Journal articles

Hao, Yue, Liu, Haowen, Zeng, Xian-Ting, Wang, Ya, Zeng, Wan-Xin, Qian, Kang-Ying, Li, Lei, Chi, Ming-Xuan, Gao, Shangbang, Hu, Zhitao and Tong, Xia-Jing (2023). UNC-43/CaMKII-triggered anterograde signals recruit GABAARs to mediate inhibitory synaptic transmission and plasticity at C. elegans NMJs. Nature Communications, 14 (1) 1436, 1-15. doi: 10.1038/s41467-023-37137-0

Zhang, Li, Li, Lei, Wei, Ziqing, Zhou, Hao, Liu, Haowen, Wang, Shen, Ren, Yijing, Dai, Tiankai, Wang, Jiafan, Hu, Zhitao and Ma, Cong (2023). The C2 and PH domains of CAPS constitute an effective PI(4,5)P2-binding unit essential for Ca2+-regulated exocytosis. Structure, 31 (4), 424-434.e6. doi: 10.1016/j.str.2023.02.004

Li, Lei, Liu, Haowen, Qian, Kang-Ying, Nurrish, Stephen, Zeng, Xian-Ting, Zeng, Wan-Xin, Wang, Jiafan, Kaplan, Joshua M., Tong, Xia-Jing and Hu, Zhitao (2022). CASK and FARP localize two classes of post-synaptic ACh receptors thereby promoting cholinergic transmission. PLOS Genetics, 18 (10) e1010211, e1010211. doi: 10.1371/journal.pgen.1010211

Shao, Zhiyong, Yang, Yang and Hu, Zhitao (2022). Editorial: regulation of synaptic structure and function. Frontiers in Molecular Neuroscience, 15 1060367, 1-4. doi: 10.3389/fnmol.2022.1060367

Xue, Renhao, Meng, Hao, Yin, Jiaxiang, Xia, Jingyao, Hu, Zhitao and Liu, Huisheng (2021). The Role of Calmodulin vs. Synaptotagmin in Exocytosis. Frontiers in Molecular Neuroscience, 14 691363, 1-12. doi: 10.3389/fnmol.2021.691363

Qian K. Y., Zeng W. X., Hao Y., Zeng X. T., Liu H., Li L., Chen L., Tian F. M., Chang C., Hall Q., Song C. X., Gao S., Hu Z., Kaplan J. M., Li Q., and Tong X. J. Male pheromones modulate synaptic transmission at the C. elegans neuromuscular junction in a sexually dimorphic manner. eLife 10, (2021).

Padmanarayana M., Liu H., Michelassi F., Li L., Betensky D., Dominguez M. J., Sutton R. B., Hu Z., and Dittman J. S. A unique C2 domain at the C terminus of Munc13 promotes synaptic vesicle priming. Proceedings of the National Academy of Sciences of the United States of America 118, (2021).

Liu H., Li L., Sheoran S., Yu Y., Richmond J. E., Xia J., Tang J., Liu J., and Hu Z. The M domain in UNC-13 regulates the probability of neurotransmitter release. Cell Reports 34, 108828, (2021).

Liu H., Li L., Krout M., Sheoran S., Zhao Q., Chen J., Liu H., Richmond J. E., and Hu Z. Protocols for electrophysiological recordings and electron microscopy at C. elegans neuromuscular junction. STAR Protoc 2, 100749, (2021).

Li L., Liu H., Krout M., Richmond J. E., Wang Y., Bai J., Weeratunga S., Collins B. M., Ventimiglia D., Yu Y., Xia J., Tang J., Liu J., and Hu Z. A novel dual Ca2+ sensor system regulates Ca2+-dependent neurotransmitter release. The Journal of Cell Biology 220, (2021).

Snieckute G., Baltaci O., Liu H., Li L., Hu Z., and Pocock R. mir-234 controls neuropeptide release at the Caenorhabditis elegans neuromuscular junction. Molecular and cellular neurosciences 98, 70-81, (2019).

Liu H., Li L., Nedelcu D., Hall Q., Zhou L., Wang W., Yu Y., Kaplan J. M., and Hu Z. Heterodimerization of UNC-13/RIM regulates synaptic vesicle release probability but not priming in C. elegans. eLife 8, (2019).

Li L., Liu H., Hall Q., Wang W., Yu Y., Kaplan J. M., and Hu Z. A hyperactive form of unc-13 enhances Ca2+ sensitivity and synaptic vesicle release probability in C. elegans. Cell Reports 28, 2979-2995 e2974, (2019).

Tikiyani V., Li L., Sharma P., Liu H., Hu Z., and Babu K. Wnt secretion is regulated by the tetraspan protein HIC-1 through its interaction with neurabin/NAB-1. Cell Reports 25, 1856-1871 e1856, (2018).

Sharma P., Li L., Liu H., Tikiyani V., Hu Z.*, and Babu K.*. The Claudin-like protein HPO-30 is required to maintain LAChRs at the C. elegans neuromuscular junction. The Journal of Neuroscience 38, 7072-7087, (2018). (*, corresponding authors)

Liu H., Li L., Wang W., Gong J., Yang X., and Hu Z. Spontaneous vesicle fusion is differentially regulated at cholinergic and GABAergic synapses. Cell Reports 22, 2334-2345, (2018).

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

Tong X. J., Lopez-Soto E. J., Li L., Liu H., Nedelcu D., Lipscombe D., Hu Z., and Kaplan J. M. Retrograde synaptic inhibition is mediated by alpha-neurexin binding to the alpha2delta subunits of N-type calcium channels. Neuron 95, 326-340 e325, (2017).

Michelassi F., Liu H., Hu Z., and Dittman J. S. A C1-C2 module in Munc13 inhibits calcium-dependent neurotransmitter release. Neuron 95, 577-590 e575, (2017).

Du H., Zhang M., Yao K., and Hu Z. 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, (2017).

Tong X. J.*, Hu Z.*, Liu Y., Anderson D., and Kaplan J. M. A network of autism linked genes stabilizes two pools of synaptic GABAA receptors. eLife 4, e09648, (2015). (*, first authors)

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

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

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

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

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

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

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

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

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

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

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

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

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

Hu Z., Dun X., Zhang M., Zhu H., Xie L., Wu Z., Chen Z., and 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 50, 285-291, (2007).

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

Hu Z., Zhao P., Liu J., Wu Z. X., and Xu T. Alpha-latrotoxin triggers extracellular Ca(2+)-dependent exocytosis and sensitizes fusion machinery in endocrine cells. Acta Biochim Biophys Sin (Shanghai) 38, 8-14, (2006).

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

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


Xue R., Meng H., Yin J., Xia J., Hu Z., and Liu H. The role of calmodulin vs. synaptotagmin in exocytosis. Frontiers in Molecular

Neuroscience 14, 691363, (2021).

Book chapters

Frederic M., and Hu Z. Functional roles of UNC-13/Munc13 and UNC- 18/Munc18 in neurotransmission. Molecular Mechanisms of Neurotransmitter Release-Advances in Neurobiology. Springer Nature. In press, (2022).

Gao SB, Hu, Z. In vivo recordings at Caenorhabditis elegans neuromuscular junction. Extracellular Recording Approaches-Springer Nature 134, (2018).

  • 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

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

Our team

Group Leader

Research Members

  • Haowen Liu

    Mr Haowen Liu

    Postdoctoral Research Fellow
    Queensland Brain Institute
  • Ray (Lei) Li

    Dr Lei Li

    Postdoctoral Research Fellow
    Queensland Brain Institute