Synaptic neurobiology

About

excitatory synaptic transmission in the mammalian central nervous system. The ability of neurons to modulate the strength of their connections, termed synaptic plasticity, is determined in part by the number of these receptors at synapses. Dysregulation of AMPA receptor trafficking results in an imbalance in neuronal excitation and inhibition, which often results in the memory impairment and cognitive deficits associated with various neurological disorders, such as Alzheimer’s disease, schizophrenia, bipolar disorders and autism. The major aim of the Anggono group is to understand the detailed molecular mechanisms regulating AMPA receptor trafficking, synaptic plasticity, learning and memory. 

In 2015, the Anggono group discovered that all four AMPA receptor subunits (GluA1-4) undergo post-translational ubiquitination in an activity-dependent manner. They mapped the sites of ubiquitination to specific lysine residues in the carboxyl-terminal tails of GluA1 and GluA2 subunits. Mutation of these lysine residues inhibits AMPA receptor ubiquitination, subsequently leading to mis-sorting of AMPA receptors from late- to recycling-endosomes. As a consequence, these mutant AMPA receptors escape the degradation pathway and are more stable in neurons.

This study, which was published in the journal Cell Reports, has wide-ranging ramifications, including for our understanding of several neurological disorders by which AMPA receptors are aberrantly degraded, such as Alzheimer’s disease and schizophrenia. This paper was recommended by the Faculty of 1000 and formed the subject of invited seminars at the 25th Meeting of the International Society for Neurochemistry (Cairns, Australia) and the 14th Federation of Asian and Oceanian Biochemists and Molecular Biologists Congress (Hyderabad, India). Work in the Anggono laboratory was supported by project grants from the NHMRC and the Alzheimer’s Australia Dementia Research Foundation.

Group Publications

Research Areas

  • Neuronal trafficking
  • Neuroepigenetics
  • Glutamate receptors
  • Synaptic vesicle recycling
  • Endosomal sorting
  • Neurodegenerative diseases


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Group Leader

  • Dr Victor Anggono

    Group Leader in Dementia Reseach
    Clem Jones Centre for Ageing Dementia Research

Research Members

  • Dr Jocelyn Widagdo

    ARC DECRA Research Fellow
    Clem Jones Centre for Ageing Dementia Research
  • Dr Men Tan

    Research Assistant
    Queensland Brain Institute
  • Dr Iris Wang

    ARC DECRA Research Fellow
    Clem Jones Centre for Ageing Dementia Research
  • Hilary Yong

    Ms Hilary Yong

    Research Assistant
    Queensland Brain Institute

Students

  • Miss Sumasri Guntupalli

    PhD student
    Queensland Brain Institute
    Casual Phys/Pharm Academic
    School of Biomedical Sciences
  • Miss Joanne Jang

    PhD Student
    Queensland Brain Institute
    Casual Academic Phys/Pharm
    School of Biomedical Sciences

 

A molecular code for endosomal recycling of phosphorylated cargos by the SNX27–retromer complex

Clairfeuille, Thomas, Mas, Caroline, Chan, Audrey S. M., Yang, Zhe, Tello-Lafoz, Maria, Chandra, Mintu, Wigagdo, Jocelyn, Kerr, Markus, Blessy, Paul, Merida, Isabel, Teasdale, Rohan D., Pavlos, Nathan J., Anggono, Victor and Collins, Brett (2016) A molecular code for endosomal recycling of phosphorylated cargos by the SNX27–retromer complex. Nature Structural and Molecular Biology23 10: 921-932. doi:10.1038/nsmb.3290

Activity-Dependent ubiquitination of GluA1 and GluA2 regulates AMPA receptor intracellular sorting and degradation

Widagdo, Jocelyn, Chai, Ye Jin, Ridder, Margreet C, Chau, Yu Qian, Johnson, Richard C, Sah, Pankaj, Huganir, Richard L and Anggono, Victor (2015) Activity-Dependent ubiquitination of GluA1 and GluA2 regulates AMPA receptor intracellular sorting and degradation. Cell Reports10 5: 783-795. doi:10.1016/j.celrep.2015.01.015

PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression

Anggono, Victor, Koc-Schmitz, Yeliz, Widagdo, Jocelyn, Kormann, Jan, Quan, Annie, Chen, Chih-Ming, Robinson, Phillip J., Choi, Se-Young, Linden, David J., Plomann, Markus and Huganir, Richard L. (2013) PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression. Proceedings of the National Academy of Sciences of the United States of America110 34: 13976-13981. doi:10.1073/pnas.1312467110

Regulation of AMPA receptor trafficking and synaptic plasticity

Anggono, Victor and Huganir, Richard L. (2012) Regulation of AMPA receptor trafficking and synaptic plasticity.Current Opinion in Neurobiology22 3: 461-469. doi:10.1016/j.conb.2011.12.006

Regulation of AMPA receptor function by the human memory-associated gene KIBRA

Makuch, Lauren, Volk, Lenora, Anggono, Victor, Johnson, Richard C., Yu, Yilin, Duning, Kerstin, Kremerskothen, Joachim, Xia, Jun, Takamiya, Kogo and Huganir, Richard L. (2011) Regulation of AMPA receptor function by the human memory-associated gene KIBRA. Neuron71 6: 1022-1029. doi:10.1016/j.neuron.2011.08.017

PICK1 Loss of Function Occludes Homeostatic Synaptic Scaling

Anggono, Victor, Clem, Roger L. and Huganir, Richard L. (2011) PICK1 Loss of Function Occludes Homeostatic Synaptic Scaling. Journal of Neuroscience31 6: 2188-2196. doi:10.1523/JNEUROSCI.5633-10.2011

Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis

Anggono, V, Smillie, KJ, Graham, ME, Valova, VA, Cousin, MA and Robinson, PJ (2006) Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis. Nature Neuroscience9 6: 752-760. doi:10.1038/nn1695

 

Journal Articles

A molecular code for endosomal recycling of phosphorylated cargos by the SNX27–retromer complex

Clairfeuille, Thomas, Mas, Caroline, Chan, Audrey S. M., Yang, Zhe, Tello-Lafoz, Maria, Chandra, Mintu, Wigagdo, Jocelyn, Kerr, Markus, Blessy, Paul, Merida, Isabel, Teasdale, Rohan D., Pavlos, Nathan J., Anggono, Victor and Collins, Brett (2016) A molecular code for endosomal recycling of phosphorylated cargos by the SNX27–retromer complex. Nature Structural and Molecular Biology23 10: 921-932. doi:10.1038/nsmb.3290

PACSIN1 regulates the dynamics of AMPA receptor trafficking

Widagdo, Jocelyn, Fang, Huaqiang, Jang, Se Eun and Anggono, Victor (2016) PACSIN1 regulates the dynamics of AMPA receptor trafficking. Scientific Reports6 31070: 1-9. doi:10.1038/srep31070

Experience-dependent accumulation of N6-methyladenosine in the prefrontal cortex is associated with memory processes in mice

Widagdo, Jocelyn, Zhao, Qiong-Yi, Kempen, Marie-Jeanne, Tan, Men Chee, Ratnu, Vikram S., Wei, Wei, Leighton, Laura, Spadaro, Paola A., Edson, Janette, Anggono, Victor and Bredy, Timothy W. (2016) Experience-dependent accumulation of N6-methyladenosine in the prefrontal cortex is associated with memory processes in mice. Journal of Neuroscience36 25: 6771-6777. doi:10.1523/JNEUROSCI.4053-15.2016

DGKθ Catalytic Activity Is Required for Efficient Recycling of Presynaptic Vesicles at Excitatory Synapses

Goldschmidt, Hana L., Tu-Sekine, Becky, Volk, Lenora, Anggono, Victor, Huganir, Richard L. and Raben, Daniel M. (2016) DGKθ Catalytic Activity Is Required for Efficient Recycling of Presynaptic Vesicles at Excitatory Synapses. Cell Reports14 2: 200-207. doi:10.1016/j.celrep.2015.12.022

Amyloid-β-induced dysregulation of AMPA receptor trafficking

Guntupalli, Sumasri, Widagdo, Jocelyn and Anggono, Victor (2016) Amyloid-β-induced dysregulation of AMPA receptor trafficking. Neural Plasticity2016 1-12. doi:10.1155/2016/3204519

Glutamate receptors in alzheimer's disease: mechanisms and therapies

Anggono, Victor, Tsai, Li-Huei and Goetz, Juergen (2016) Glutamate receptors in alzheimer's disease: mechanisms and therapies. Neural Plasticity2016 . doi:10.1155/2016/8256196

Ubiquitin signals the demise of AMPA receptors

Widagdo, Jocelyn and Anggono, Victor (2015) Ubiquitin signals the demise of AMPA receptors. Oncotarget6 18: 15718-15719.

Activity-Dependent ubiquitination of GluA1 and GluA2 regulates AMPA receptor intracellular sorting and degradation

Widagdo, Jocelyn, Chai, Ye Jin, Ridder, Margreet C, Chau, Yu Qian, Johnson, Richard C, Sah, Pankaj, Huganir, Richard L and Anggono, Victor (2015) Activity-Dependent ubiquitination of GluA1 and GluA2 regulates AMPA receptor intracellular sorting and degradation. Cell Reports10 5: 783-795. doi:10.1016/j.celrep.2015.01.015

Sorting Nexin 27 regulates basal and activity-dependent trafficking of AMPARs

Hussain, Natasha K., Diering, Graham H., Sole, Jonathan, Anggono, Victor and Huganir, Richard L. (2014) Sorting Nexin 27 regulates basal and activity-dependent trafficking of AMPARs. Proceedings of the National Academy of Sciences of the United States of America111 32: 11840-11845. doi:10.1073/pnas.1412415111

AMPA receptor pHluorin-GluA2 reports NMDA receptor-induced intracellular acidification in hippocampal neurons

Rathje, Mette, Fang, Huaqiang, Bachman, Julia L., Anggono, Victor, Gether, Ulrik, Huganir, Richard L. and Madsen, Kenneth L. (2013) AMPA receptor pHluorin-GluA2 reports NMDA receptor-induced intracellular acidification in hippocampal neurons. Proceedings of the National Academy of Sciences of the United States of America110 35: 14426-14431. doi:10.1073/pnas.1312982110

PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression

Anggono, Victor, Koc-Schmitz, Yeliz, Widagdo, Jocelyn, Kormann, Jan, Quan, Annie, Chen, Chih-Ming, Robinson, Phillip J., Choi, Se-Young, Linden, David J., Plomann, Markus and Huganir, Richard L. (2013) PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression. Proceedings of the National Academy of Sciences of the United States of America110 34: 13976-13981. doi:10.1073/pnas.1312467110

Regulation of AMPA receptor trafficking and synaptic plasticity

Anggono, Victor and Huganir, Richard L. (2012) Regulation of AMPA receptor trafficking and synaptic plasticity.Current Opinion in Neurobiology22 3: 461-469. doi:10.1016/j.conb.2011.12.006

Phosphorylation of syndapin I F-BAR domain at two helix-capping motifs regulates membrane tubulation

Quana, Annie, Xue, Jing, Wielens, Jerome, Smillie, Karen J., Anggono, Victor, Parker, Michael W., Cousin, Michael A., Graham, Mark E. and Robinson, Phillip J. (2012) Phosphorylation of syndapin I F-BAR domain at two helix-capping motifs regulates membrane tubulation. Proceedings of the National Academy of Sciences of the United States of America109 10: 3760-3765. doi:10.1073/pnas.1108294109

Phosphorylation of dynamin II at serine-764 is associated with cytokinesis

Chircop, Megan, Sarcevic, Boris, Larsen, Martin R., Malladi, Chandra S., Chau, Ngoc, Zavortink, Michael, Smith, Charlotte M., Quan, Annie, Anggono, Victor, Hains, Peter G., Graham, Mark E. and Robinson, Phillip J. (2011) Phosphorylation of dynamin II at serine-764 is associated with cytokinesis. Biochimica Et Biophysica Acta-Molecular Cell Research1813 10: 1689-1699. doi:10.1016/j.bbamcr.2010.12.018

Regulation of AMPA receptor function by the human memory-associated gene KIBRA

Makuch, Lauren, Volk, Lenora, Anggono, Victor, Johnson, Richard C., Yu, Yilin, Duning, Kerstin, Kremerskothen, Joachim, Xia, Jun, Takamiya, Kogo and Huganir, Richard L. (2011) Regulation of AMPA receptor function by the human memory-associated gene KIBRA. Neuron71 6: 1022-1029. doi:10.1016/j.neuron.2011.08.017

Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism

Mejias, Rebeca, Adamczyk, Abby, Anggono, Victor, Niranjan, Tejasvi, Thomas, Gareth M., Sharma, Kamal, Skinner, Cindy, Schwartz, Charles E., Stevenson, Roger E., Fallin, M. Daniele, Kaufmann, Walter, Pletnikov, Mikhail, Valle, David, Huganir, Richard L. and Wang, Tao (2011) Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism. Proceedings of the National Academy of Sciences of the United States of America108 12: 4920-4925. doi:10.1073/pnas.1102233108

PICK1 Loss of Function Occludes Homeostatic Synaptic Scaling

Anggono, Victor, Clem, Roger L. and Huganir, Richard L. (2011) PICK1 Loss of Function Occludes Homeostatic Synaptic Scaling. Journal of Neuroscience31 6: 2188-2196. doi:10.1523/JNEUROSCI.5633-10.2011

PICK1 Regulates Incorporation of Calcium-Permeable AMPA Receptors during Cortical Synaptic Strengthening

Clem, Roger L., Anggono, Victor and Huganir, Richard L. (2010) PICK1 Regulates Incorporation of Calcium-Permeable AMPA Receptors during Cortical Synaptic Strengthening. Journal of Neuroscience30 18: 6360-6366. doi:10.1523/JNEUROSCI.6276-09.2010

Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD

Thorsen, Thor S., Madsen, Kenneth L., Rebola, Nelson, Rathje, Mette, Anggono, Victor, Bach, Anders, Moreira, Irina S., Stuhr-Hansen, Nicolai, Dyhring, Tino, Peters, Dan, Beuming, Thijs, Huganir, Richard, Weinstein, Harel, Mulle, Christophe, Stromgaard, Kristian, Ronn, Lars Christian B. and Gether, Ulrik (2010) Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD. Proceedings of the National Academy of Sciences of the United States of America107 1: 413-418. doi:10.1073/pnas.0902225107

The Phospho-Dependent Dynamin-Syndapin Interaction Triggers Activity-Dependent Bulk Endocytosis of Synaptic Vesicles

Clayton, Emma L., Anggono, Victor, Smillie, Karen J., Chau, Ngoc, Robinson, Phillip J. and Cousin, Michael A. (2009) The Phospho-Dependent Dynamin-Syndapin Interaction Triggers Activity-Dependent Bulk Endocytosis of Synaptic Vesicles. Journal of Neuroscience29 24: 7706-7717. doi:10.1523/JNEUROSCI.1976-09.2009

Syndapin I and endophilin I bind overlapping proline-rich regions of dynamin I: role in synaptic vesicle endocytosis

Anggono, Victor and Robinson, Phillip J. (2007) Syndapin I and endophilin I bind overlapping proline-rich regions of dynamin I: role in synaptic vesicle endocytosis. Journal of Neurochemistry102 3: 931-943. doi:10.1111/j.1471-4159.2007.04574.x

The in vivo phosphorylation sites of rat brain dynamin I

Graham, Mark E., Anggono, Victor, Bache, Nicolai, Larsen, Martin R., Craft, George E. and Robinson, Phillip J. (2007) The in vivo phosphorylation sites of rat brain dynamin I. Journal of Biological Chemistry282 20: 14695-14707. doi:10.1074/jbc.M609713200

Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis

Anggono, V, Smillie, KJ, Graham, ME, Valova, VA, Cousin, MA and Robinson, PJ (2006) Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis. Nature Neuroscience9 6: 752-760. doi:10.1038/nn1695

Control of synaptic vesicle endocytosis by dephosphorylation of dynamin I

Robinson, P. J., Anggono, V. and Cousin, M. A. (2006) Control of synaptic vesicle endocytosis by dephosphorylation of dynamin I. Neurosignals15 1: 49-49.

Dr Victor Anggono

  • Young Scientist Award, The Federation of Asian and Oceanian Biochemists and Molecular Biologists (2015) 
  • Science to Art Award, NHMRC (2015)
  • Boomerang Award, Australian Society for Biochemistry and Molecular Biology (2011)

Dr Iris Wang

  • ARC Discovery Early Career Researcher Award (2017-2019)
  • JG Russell Award, Australian Academy of Science (2017)
  • Best Paper Award, Clem Jones Centre for Ageing Dementia Research (2016)
  • University of Queensland Postdoctoral Research Fellowship (2013-2015)

Dr Jocelyn Widagdo

  • ARC Discovery Early Career Researcher Award (2017-2019)
  • Young Investigator Travel Grant, International Society for Neurochemistry (2017)
  • The Ian Potter Foundation Travel Award (2013)
  • The Lorne Genome Travel Grant (2013)


  • Prof. Richard L. Huganir, Johns Hopkins University School of Medicine, Baltimore, USA
  • Prof. Michael A. Cousin, University of Edinburgh, UK
  • A/Prof. Melanie A. Woodin, University of Toronto, Canada
  • Prof. John McGrath, University of Queensland
  • A/Prof. Brett Collins, University of Queensland
  • A/Prof. Bruno van Swinderen, University of Queensland
  • A/Prof. Thomas Fath, University of New South Wales

 

 

 

 

 

 

 

 

 


Project 1: Regulation of postsynaptic glutamate receptor dynamics by intracellular scaffolding and signalling molecules.

Project 2: Mechanisms underlying dysregulation of postsynaptic glutamate receptor trafficking in neurodegenerative diseases.

Project 3: Regulation of synaptic function by post-translational modifications, including phosphorylation, ubiquitination and palmitoylation.

Project 4: Regulation of presynaptic vesicle recycling by BAR domain-containing proteins.

Project 5: Epitranscriptomic mechanisms of synaptic plasticity, learning and memory.

Project 6: The roles of non-coding RNAs (miRNAs and lncRNAs) in synaptic plasticity, learning and memory.

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