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.

Molecular mechanisms of postsynaptic glutamate receptor trafficking
Regulated trafficking of AMPA- and NMDA-type glutamate receptors into and out of the postsynaptic membrane is a key determinant of synaptic plasticity, a cellular correlate of learning and memory. Using a combination of biochemical, molecular biology and live-cell imaging microscopy to study the dynamics of glutamate receptors trafficking in living hippocampal neurons, our research has uncovered the roles of key intracellular scaffolding/signalling molecules in regulating glutamate receptor functions, including PICK1 (Anggono et al., Journal of Neuroscience, 2011), Syndapin/PACSIN (Anggono et al., PNAS, 2013; Widagdo et al., Scientific Reports, 2016) and SNX27 (Hussain et al., PNAS, 2014; Clairfeuille et al., Nature Structural & Molecular Biology, 2016; Mota Vieira et al., Cell Reports, 2020; and Yong et al., Cell Reports, 2021).

Our research in this field has also led to the discovery that all AMPA receptor subunits undergo activity-dependent ubiquitination, a reversible post-translational modification that regulates receptor intracellular sorting and degradation (Widagdo et al., Cell Reports, 2015). Importantly,  we also discovered that the same ubiquitination pathway underlies amyloid-β-induced loss of GluA1 from the cell surface and synaptic depression (Guntupalli et al., Journal of Biological Chemistry, 2017).

RNA Epitranscriptomics in Neurobiology
Synaptic plasticity and long-term memory require de novo gene transcription and new protein synthesis. It is now well established that these two fundamental cellular processes are tightly regulated at the level of RNA (by non-coding RNAs, post-transcriptional modification of RNAs and RNA binding proteins). In collaboration with A/Prof. Tim Bredy (QBI, UQ) and Dr. Widagdo, we were the first to demonstrate the role of m6A RNA methylation in memory consolidation (Widagdo et al., Journal of Neuroscience, 2016). Led by CI Widagdo, this work has subsequently been extended in our laboratory. We provided the first evidence for the dysregulation of m6A signalling in Alzheimer’s disease (Huang et al., eNeuro, 2020) and the aging process (Huang et al., Aging Cell, 2023). We have also provided the first demonstration of the role of the long non-coding RNA Meg3 in regulating the trafficking of AMPA receptors during synaptic potentiation (Tan and Widagdo et al., Frontiers in Cellular Neuroscience, 2017).

Our research in this field has also been extended to understanding the structure and function of RNA-binding proteins. We identified an essential role of ubiquitin signalling in regulating the proteasomal degradation and nuclear translocation of the RNA demethylase, Fto (Zhu et al., Journal of Molecular Biology, 2018). More recently, work in collaboration with Dr. Mihwa Lee (La Trobe University) has identified a structural and molecular basis of the zinc-induced cytoplasmic aggregation of the RNA binding protein SFPQ (Huang et al., Nucleic Acids Research, 2020). This work provides a novel conceptual framework on how metal-induced polymerisation of RNA-binding protein mediates cytoplasmic aggregation, a form of protein misregulation that is commonly associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (Widagdo et al., Open Biology, 2022).

Research Articles

  1. Leiter, Odette, Brici, David, Fletcher, Stephen J., Yong, Xuan Ling Hilary, Widagdo, Jocelyn, Matigian, Nicholas, Schroer, Adam B., Bieri, Gregor, Blackmore, Daniel G., Bartlett, Perry F., Anggono, Victor, Villeda, Saul A. and Walker, Tara L. (2023). Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice. Nature Communications, 14 (1) 4375, 1-20. doi: 10.1038/s41467-023-39873-9
  2. Guntupalli, Sumasri, Park, Pojeong, Han, Dae Hee, Zhang, Lingrui, Yong, Xuan Ling Hilary, Ringuet, Mitchell, Blackmore, Daniel G., Jhaveri, Dhanisha J., Koentgen, Frank, Widagdo, Jocelyn, Kaang, Bong-Kiun and Anggono, Victor (2023). Ubiquitination of the GluA1 subunit of AMPA receptors is required for synaptic plasticity, memory and cognitive flexibility. The Journal of Neuroscience, 43 (30), JN-RM. doi: 10.1523/jneurosci.1542-22.2023
  3. Leiter, Odette, Brici, David, Fletcher, Stephen J., Yong, Xuan Ling Hilary, Widagdo, Jocelyn, Matigian, Nicholas, Schroer, Adam B., Bieri, Gregor, Blackmore, Daniel G., Bartlett, Perry F., Anggono, Victor, Villeda, Saul A. and Walker, Tara L. (2023). Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice. Nature Communications, 14 (1) 4375, 1-20. doi: 10.1038/s41467-023-39873-9
  4. Radford RAW, Rayner SL, Szwaja P, Morsch M, Cheng F, Zhu T, Widagdo J, Anggono V, Pountney DL, Chung R, Lee A (2023) Identification of phosphorylated Tau protein interactors in progressive supranuclear palsy (PSP) reveals networks involved in protein degradation, stress responses, cytoskeletal dynamics, metabolic processes and neurotransmission. Journal of Neurochemistry (Accepted 23 February 2023) – In Press. 
  5. Huang H, Song R, Wong JJL, Anggono V, Widagdo J (2023) The N6-methyladenosine RNA landscape in aged mouse hippocampus. Aging Cell 22, e13755.
  6. Widagdo J, Anggono V, Wong JJ (2022) The multifaceted effects of YTHDC1-mediated nuclear m6A recognition. Trends in Genetics 38, 325-332. 
  7. Anggono V, Opazo P (2022) The making of memories. Seminars in Cell & Developmental Biology 125, 66-67. (Editorial)
  8. Widagdo J, Wong JJ, Anggono V (2022) The m6A-epitranscriptome in brain plasticity, learning and memory. Seminars in Cell & Developmental Biology 125, 110-121. 
  9. Widagdo J, Udagedara S, Bhembre N, Tan JZA, Neureiter L, Huang J, Anggono V, Lee M (2022) Familial ALS-associated SFPQ variants promote the formation of SFPQ cytoplasmic aggregates in primary neurons. Open Biology 12, 220187.
  10. Wong E, Anggono V, Williams SR, Degnan SM, Degnan BM (2022) Phototransduction in a marine sponge provides insights into the origin of animal vision. iScience 25, 104436.
  11. Ho XY, Coakley S, Amor R, Anggono V, Hilliard MA (2022) The metalloprotease ADM-4/ADAM17 promotes axonal repair. Science Advances 8, eabm2882. Recommended in Faculty Opinions.
  12. Yong, Xuan Ling Hilary, Zhang, Lingrui, Yang, Liming, Chen, Xiumin, Tan, Jing Zhi Anson, Yu, Xiaojun, Chandra, Mintu, Livingstone, Emma, Widagdo, Jocelyn, Vieira, Marta M., Roche, Katherine W., Lynch, Joseph W., Keramidas, Angelo, Collins, Brett M. and Anggono, Victor (2021). Regulation of NMDA receptor trafficking and gating by activity-dependent CaMKIIα phosphorylation of the GluN2A subunit. Cell Reports, 36 (1) 109338, 1-21. doi: 10.1016/j.celrep.2021.109338
  13. Yong XLH, Cousin MA, Anggono V (2020) PICK1 regulates activity-dependent synaptic vesicle cargo retrieval. Cell Reports 33, 108312.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. Anggono V, Clem RL, Huganir RL (2011) PICK1 loss of function occludes homeostatic synaptic scaling. Journal of Neuroscience 31, 2188-2196.
  26. 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.
  27. 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

  1. 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.  
  2. Widagdo J, Anggono V (2018) The m6A-epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity. Journal of Neurochemistry 147, 137-152.
  3. Widagdo J, Guntupalli S, Jang SE, Anggono V (2017) Regulation of AMPA receptor trafficking by protein ubiquitination. Frontiers in Molecular Neuroscience 10, 347.
  4. Guntupalli S, Widagdo J, Anggono V (2016) Amyloid-β-induced dysregulation of AMPA receptor trafficking. Neural Plasticity 2016, 3204519.
  5. Anggono V, Huganir RL (2012) Regulation of AMPA receptor trafficking and synaptic plasticity. Current Opinion in Neurobiology 22, 461-469.

View all publications

2023 - 2026 ARC Future Fellowship ( FT220100485) "Molecular basis of glutamate receptor trafficking in neuronal plasticity"

2023 - 2025 ARC Project Grant (DP230102041) "Novel role of RNA methylation in neuronal homeostasis"

2022 - 2025 ARC Project Grant "Regulation of activity-induced glutamate receptor trafficking in neurons"

2021 - 2022 Motor Neurone Disease Research Institute Australia Inc "Molecular mechanisms underlying the cytoplasmic aggregation of the RNA binding protein, SFPQ, in ALS"

2019 - 2022 ARC Project Grant (DP190101390) “Regulation of glutamate receptor dynamics in mammalian central neurons

2018 - 2021 NHMRC Project Grant (GNT1138452) “Regulation of glutamate receptor trafficking by the calcium- and lipid-binding protein, copine-6” 

2017 - 2019 ARC Project Grant (DP170102402) “Regulation of synaptic vesicle endocytosis by membrane-sensing proteins” 

2016 - 2018 NHMRC Project Grant (GNT1099114) “Sorting out the synapse: the role of intracellular trafficking in NMDA receptor homeostasis

  • 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