Dr Victor Anggono graduated from the University of New South Wales, and received his PhD in 2007 from the University of Sydney. His thesis, performed at the Children’s Medical Research Institute with Professor Phil Robinson, focused on understanding the cellular and molecular mechanisms underlying neurotransmitter release from the presynaptic nerve terminal. From 2007 through 2012, he was awarded fellowships from the International Human Frontiers Science Program and the Australian National Health and Medical Research Council to pursue his postdoctoral training at the Johns Hopkins University in Baltimore, USA. He worked with Professor Richard Huganir to study the molecular mechanisms regulating AMPA receptors trafficking and synaptic plasticity, a cellular correlate of learning and memory. In March 2012, Dr Anggono returned to Australia as a NHMRC CJ Martin Research Fellow to establish his independent research laboratory at the Clem Jones Centre for Ageing Dementia Research within the Queensland Brain Institute, the University of Queensland.
The human brain contains more than 100 billion neurons (nerve cells) that are interconnected and highly organised into ensembles of neural circuits. Efficient communication between neurons is crucial for our daily activities ranging from muscle movement and motor coordination to higher-order information processing and cognitive functions such as perception, attention, reasoning and emotions. Neuronal communication occurs at specialised structures known as synapses. Synaptic transmission depends on the ability of neurons to release chemical signals from presynaptic nerve terminal, which diffuse across the synaptic cleft and bind to postsynaptic receptors on the other neurons. Modulation of neural connectivity is critical during learning and memory, while abnormal synaptic function is linked to various neuropsychiatric disorders (bipolar disorder, depression and schizophrenia), neurodegenerative diseases (Alzheimer’s, Parkinson’s and Huntington’s diseases) and neurodevelopmental disorders (autism and intellectual disability).
The main goal of our research is to unravel the cellular and molecular mechanisms of neuronal communication in order to understand physiological phenomena such as learning, memory, behaviour and disease. In particular, we aim to uncover the molecular sequence of events underlying two major processes that are involved in efficient excitatory synaptic transmission in mammalian central neurons by combining classic biochemical and molecular biology techniques with novel proteomics and live cell imaging microscopy methods. The long-term goal of our research is to identify dysregulated signal transduction pathways that lead to synaptic dysfunctions in transgenic mouse models of Alzheimer’s and Parkinson’s diseases, in search of novel and more effective therapeutic targets.
Presynaptic vesicle recycling
Neurotransmitters are packaged inside synaptic vesicles within axonal terminals. A typical nerve terminal contains a small number of vesicles, only enough to maintain about 5-10 seconds of neurotransmission. Thus, synaptic vesicle membrane proteins and lipids must be retrieved and recycled by endocytosis in order to maintain the fidelity of synaptic transmission. We are investigating roles of BAR domain containing proteins that are capable of lipid binding in controlling synaptic vesicle recycling and how their functions are modulated by the rapid and reversible post-translational modifications, such as protein phosphorylation and ubiquitination.
Postsynaptic AMPA-type glutamate receptor trafficking
The amino acid glutamate is the major excitatory neurotransmitter in the brain. The AMPA-type glutamate receptors are the principal receptors that mediate most of the fast excitatory synaptic transmission in the mammalian brain. The dynamic trafficking and proper synaptic targeting of AMPA receptors are crucial in determining the strength and plasticity of excitatory synaptic transmission. We seek to determine the molecular mechanisms underlying the precise membrane trafficking and endosomal sorting of AMPA receptors, focusing on their regulation by novel AMPA receptor interacting proteins and post-translational modifications.
PhD and Honours projects available
If you are highly motivated and interested in pursuing graduate studies (PhD and Honours), please contact Dr Anggono (email@example.com) for more information on available projects.
- Professor Richard Huganir - The Johns Hopkins University School of Medicine, Baltimore, USA
- Professor Pankaj Sah - Queensland Brain Institute, The University of Queensland
- Professor Fred Meunier - Queensland Brain Institute, The University of Queensland
- Professor Jürgen Götz - Queensland Brain Institute, The University of Queensland
- Dr Thomas Fath - University of New South Wales
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. (Recommended by the Faculty of 1000)
Hussain NK, Diering G, Sole J, Anggono V, Huganir RL (2014) Sorting nexin 27 regulates basal and activity-dependent trafficking of AMPARs. Proceedings of the National Academy of Sciences of the USA 111, 11840-11845.
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.
Anggono V, Huganir RL (2012) Regulation of AMPA receptor trafficking and synaptic plasticity. Current Opinion in Neurobiology 22, 461-469.
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. (Highlighted in Nature Reviews Neuroscience)
Anggono V, Clem RL, Huganir RL (2011) PICK1 loss of function occludes homeostatic synaptic scaling. Journal of Neuroscience 31, 2188-2196.
Thorsen TS, Madsen KL, Rebola N, Rathje M, Anggono V, Bach A, Moreira IS, Stuhr-Hansen N, Dyhring T, Peters D, Beuming T, Huganir R, Weinstein H, Mulle C, Strømgaard K, Rønn LCB, Gether U (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 USA 107, 413-418. (Recommended by the Faculty of 1000)
Clayton EM, Anggono V, Smillie KJ, Chau N, Robinson PJ, Cousin MA (2009) The phospho-dependent dynamin-syndapin interaction triggers activity-dependent bulk synaptic vesicle endocytosis. Journal of Neuroscience 29, 7706-7717.
Anggono V, Robinson PJ (2007) Syndapin I and endophilin I bind to overlapping proline-rich regions of dynamin I: Role in synaptic vesicle endocytosis. Journal of Neurochemistry 102, 931-943.
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. (Recommended by the Faculty of 1000)