Synaptic neurobiology

Billions of neurons in the human brain are organised into highly interconnected neural circuits for efficient processing of sensory information.

Communication between nerve cells depends on transmission of chemical signals, which occurs at specialised structures called synapses.The ability of neurons to modulate the strength of their synaptic connections, known as synaptic plasticity, forms the cellular basis of learning and memory.

How neurons dynamically modulate their synaptic strength is one of the outstanding and most fascinating questions in modern neuroscience. To answer this question, our laboratory focusses on mechanisms that regulate neuronal trafficking (both pre- and post-synaptic membrane trafficking), as well as the epitranscriptomic (RNA modification) mechanisms underlying activity-dependent gene expression during synaptic plasticity, learning and memory. Ultimately, we aim to understand how dysregulation of these cellular processes contributes to neurological disorders and neurodegenerative diseases.

Group leader

Dr Victor Anggono

Group Leader, Synaptic Neurobiology

Senior Research Fellow

+61 7 3346 6325
+61 7 3346 6417
v.anggono@uq.edu.au
UQ Researcher Profile

We discovered the role of the protein interacting with C-kinase 1 (PICK1), the only protein with a PDZ protein-protein interaction domain and a BAR lipid-binding/dimerization domain, in regulating the pre-synaptic cargo retrieval (Yong et al., Cell Rep., 2020).
We provided the first evidence for a role of a long non-coding RNA, Meg3, in regulating the trafficking of AMPA receptors during synaptic potentiation (Tan and Widagdo et al., Front. Cell. Neurosci., 2017).
We discovered that all AMPA receptor subunits undergo activity-dependent ubiquitination to regulate receptor intracellular sorting and degradation (Widagdo et al., Cell Rep., 2015). We subsequently showed that the same ubiquitination pathway underlies amyloid-β-induced loss of the GluA1 subunit and synaptic depression (Guntupalli et al., J. Biol. Chem., 2017).

Research Articles

Yong XLH, Cousin MA, Anggono V (2020) PICK1 regulates activity-dependent synaptic vesicle cargo retrieval. Cell Reports 33, 108312.
Huang H, Camats-Perna J, Medeiros R, Anggono V, Widagdo J (2020) Altered expression of the m6A methyltransferase METTL3 in Alzheimer’s disease. eNeuro 7, ENEURO.0125-20.2020.
Vieira MM, Nguyen T, Wu K, Badger II JD, Collins BM, Anggono V, Lu W, Roche KW (2020) An epilepsy-associated GRIN2A rare variant disrupts CaMKIIα phosphorylation of GluN2A and NMDA receptor trafficking. Cell Reports 32, 108104.
Huang J, Ringuet M, Whitten A, Caria S, Lim YW, Badhan R, Anggono V, Lee M (2020) Structural basis of the zinc-induced cytoplasmic accumulation of the RNA-binding protein SFPQ. Nucleic Acids Research 48, 3356-3365.
Bademosi AT, Steeves J, Karunanithi S, Zalucki OH, Gormal RS, Liu S, Lauwers E, Verstreken P, Anggono V, Meunier FA, van Swinderen B (2018) Trapping of syntaxin1A in presynaptic nanoclusters by a clinically relevant general anesthetic. Cell Reports 22, 427-440.
Tan MC, Widagdo J, Chau YQ, Zhu T, Wong JJ, Cheung A, Anggono V (2017) The activity-induced long non-coding RNA Meg3 modulates AMPA receptor surface expression in primary cortical neurons. Frontiers in Cellular Neuroscience 11, 124.
Guntupalli S, Jang SE, Zhu T, Huganir RL, Widagdo J, Anggono V (2017) GluA1 subunit ubiquitination mediates amyloid-β-induced loss of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Journal of Biological Chemistry 292, 8186-8194
Clairfeuille T, Mas C, Chan AS, Yang Z, Tello-Lafoz M, Chandra M, Widagdo J, Kerr MC, Paul B, Mérida I, Teasdale RD, Pavloz NJ, Anggono V, Collins BM (2016) A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex. Nature Structural & Molecular Biology 23, 921-932.
Widagdo J, Zhao QY, Kempen MJ, Tan MC, Ratnu VS, Wei W, Leighton L, Spadaro PA, Edson J, Anggono V, Bredy TW (2016) Experience-dependent accumulation of N6-methyladenosine in the prefrontal cortex is associated with memory processes in mice. Journal of Neuroscience 36, 6771-6777.
Widagdo J, Chai YJ, Ridder MC, Chau YQ, Johnson RC, Sah P, Huganir RL, Anggono V (2015) Activity-dependent ubiquitination of GluA1 and GluA2 regulates AMPA receptor intracellular trafficking and degradation. Cell Reports 10, 783-795.
Anggono V, Koç-Schmitz Y, Widagdo J, Kormann J, Quan A, Chen CM, Robinson PJ, Choi SY, Linden DJ, Plomann M, Huganir RL (2013) PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression. Proceedings of the National Academy of Sciences of the USA 110, 13976-13981.
Makuch L, Volk L, Anggono V, Johnson RC, Yu Y, Duning K, Kremerskothen J, Xia J, Takamiya K, Huganir RL (2011) Regulation of AMPA receptor function by memory-associated gene KIBRA. Neuron 71, 1022-1029.
Anggono V, Clem RL, Huganir RL (2011) PICK1 loss of function occludes homeostatic synaptic scaling. Journal of Neuroscience 31, 2188-2196.
Clayton EM, Anggono V, Smillie KJ, Chau N, Robinson PJ, Cousin MA (2009) The phospho-dependent dynamin-syndapin interaction triggers activity-dependent bulk endocytosis of synaptic vesicles. Journal of Neuroscience 29, 7706-7717.
Anggono V, Smillie KJ, Graham ME, Valova VA, Cousin MA, Robinson PJ (2006) Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis. Nature Neuroscience 9, 752-760.

Review Articles

Vieira M, Yong XLH, Roche KW, Anggono V (2020) Regulation of NMDA glutamate receptor functions by the GluN2 subunits. Journal of Neurochemistry 154, 121-143.
Widagdo J, Anggono V (2018) The m6A-epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity. Journal of Neurochemistry 147, 137-152.
Widagdo J, Guntupalli S, Jang SE, Anggono V (2017) Regulation of AMPA receptor trafficking by protein ubiquitination. Frontiers in Molecular Neuroscience 10, 347.
Guntupalli S, Widagdo J, Anggono V (2016) Amyloid-β-induced dysregulation of AMPA receptor trafficking. Neural Plasticity 2016, 3204519.
Anggono V, Huganir RL (2012) Regulation of AMPA receptor trafficking and synaptic plasticity. Current Opinion in Neurobiology 22, 461-469.

View all publications

ARC Project Grant (DP190101390) “Regulation of glutamate receptor dynamics in mammalian central neurons” (2019-2022).
NHMRC Project Grant (GNT1138452) “Regulation of glutamate receptor trafficking by the calcium- and lipid-binding protein, copine-6” (2018-2021).
ARC Project Grant (DP170102402) “Regulation of synaptic vesicle endocytosis by membrane-sensing proteins” (2017-2019).
NHMRC Project Grant (GNT1099114) “Sorting out the synapse: the role of intracellular trafficking in NMDA receptor homeostasis” (2016-2018)

Activity-dependent regulation of glutamate receptor trafficking
Epitranscriptomic regulation of synaptic plasticity, learning and memory

Structure and function analysis of synaptic proteins
Neuronal trafficking in pre- and post-synaptic compartments
Post-translational regulation of synaptic function
Regulation of activity-dependent gene expression by post-transcriptional RNA methylation
RNA biology of neuronal plasticity

Our approach

Our research combines biochemical, molecular and cellular biology in both cell culture (primary neurons and cell lines) and mouse models. We utilise gene editing technology, cutting-edge microscopy, proteomics, next-generation sequencing and behavioural analyses in our study. We are particularly interested in understanding the complex neuronal signalling cascades through protein-protein interactions and post-translational modifications of key synaptic molecules.

Aims to achieve

Neurons are inherently plastic and have the ability to modify their synaptic strength and connectivity, as well as adjusting their intrinsic excitability. Our lab is interested in understanding the underlying mechanisms from the regulation of neuronal trafficking to the control of activity-dependent gene expression.