Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking.

By Shoaib Chowdhury, J. Shepherd, H. Okuno, G. Lyford, R. Petralia, N. Plath, Dietmar Kuhl, Richard L. Huganir, P. Worley. Neuron, 2006

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Arc/Arg3.1 is an immediate-early gene whose mRNA is rapidly transcribed and targeted to dendrites of neurons as they engage in information processing and storage. Moreover, Arc/Arg3.1 is known to be required for durable forms of synaptic plasticity and learning. Despite these intriguing links to plasticity, Arc/Arg3.1's molecular function remains enigmatic. Here, we demonstrate that Arc/Arg3.1 protein interacts with dynamin and specific isoforms of endophilin to enhance receptor endocytosis. Arc/Arg3.1 selectively modulates trafficking of AMPA-type glutamate receptors (AMPARs) in neurons by accelerating endocytosis and reducing surface expression. The Arc/Arg3.1-endocytosis pathway appears to regulate basal AMPAR levels since Arc/Arg3.1 KO neurons exhibit markedly reduced endocytosis and increased steady-state surface levels. These findings reveal a novel molecular pathway that is regulated by Arc/Arg3.1 and likely contributes to late-phase synaptic plasticity and memory consolidation.

Subfields: Cell Biology, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/abcde17017f26974cb72b7b737a88dcf738358aa

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Citations in the corpus

Long-term Synaptic Plasticity: Circuit Perturbation and Stabilization (2014, background): “Studies of Arc provide a model in which homeostatic plasticity as a non-Hebbian plasticity and Hebbian plasticity may show mechanistic similarities [13,21,24].”
Dendritic mRNA: transport, translation and function (2007, background): “Recently, Arc was found to mediate homeostatic synaptic scaling of AMPA receptor transmission through its ability to activate a specific AMPA receptor endocytic pathwa”
The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission (2011, background): “, an immediate early gene that has a key role in activity-dependent synaptic modificatio”
Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA receptors. (2006, background): “Since this region is also required for downregulation of AMPARs (Chowdhury et al., 2006), these data provide compelling evidence that Arc/Arg3.”
Homeostatic synaptic plasticity: local and global mechanisms for stabilizing neuronal function. (2012, background): “from the membrane (Chowdhury et al. 2006), TNFa directly increases synaptic AMPAR accumulation (Beattie et al.”
Translational control of long-lasting synaptic plasticity and memory. (2009, positive): “1 is in the endocytosis of AMPA receptors associated with LTD and the homeostatic response of neurons (Chowdhury et al., 2006; Rial Verde et al., 2006).”
The cell biology of synaptic plasticity: AMPA receptor trafficking. (2007, background): “Arc regulates AMPAR trafficking by interacting with the integral endocytic proteins dynamin and endophilin (Chowdhury et al. 2006, Rial Verde et al. 2006).”
The Angelman Syndrome-associated ubiquitin ligase Ube3A regulates synapse development by ubiquitinating Arc (2010, neutral): “Surface GluR1 Staining Immunostaining of surface GluR1 receptors was performed as previously described (Chowdhury et al., 2006).”
Calmodulin-Kinases: Modulators of Neuronal Development and Plasticity (2008, neutral): “1, which promotes AMPAR endocytosis through interaction with endophilin 2/3 and dynamin (Chowdhury et al., 2006), is rapidly (5 min) enhanced by CaMKIII phosphorylation of eEF2 (Park et al., 2008).”
Regulatory mechanisms of AMPA receptors in synaptic plasticity (2007, background): “1 ), an immediate-early gene that regulates components of the endocytosis machinery (namely endophilin 3 and dynamin 2), can contribute to homeostatic scaling by regulating endocytosis of GluR2-/GluR3-containing AMPAR”
The Self-Tuning Neuron: Synaptic Scaling of Excitatory Synapses (2008, background): “…the discussion below, I describe our current state of understanding about what aspect of neuronal or network activity is sensed by neurons during homeostatic synaptic scaling, the signaling pathways that are triggered by this change in activity, and how changes in synaptic strength are implemented.”