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Arc controls AMPAR endocytosis through a direct interaction with clathrin-adaptor protein 2
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DaSilva, Luis L., Wall, Mark J., Almeida, Luciana P. de , Wauters, Sandrine, Januario, Yunan C., Müller, Jürgen and Corrêa, Sônia A. L. (2016) Arc controls AMPAR endocytosis through a direct interaction with clathrin-adaptor protein 2. eNeuro, 3 (3). 0144-15.2016. doi:10.1523/ENEURO.0144-15.2016
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Official URL: http://dx.doi.org/10.1523/ENEURO.0144-15.2016
Abstract
The activity-regulated cytoskeleton-associated (Arc) protein control synaptic strength by facilitating AMPA receptor (AMPAR) endocytosis. Here we demonstrate that Arc targets AMPAR to be internalized through a direct interaction with the clathrin-adaptor protein 2 (AP-2). We show that Arc overexpression overexpression in dissociated hippocampal neurons obtained from C57BL/6 mouse reduces the density of AMPAR GluA1 subunits at the cell surface and reduces the amplitude and rectification of AMPAR-mediated miniature-excitatory postsynaptic currents (mEPSC). Mutations of Arc, that prevent the AP-2 interaction reduce Arc-mediated endocytosis of GluA1 and abolish the reduction in AMPAR-mediated mEPSC amplitude and rectification. Depletion of the AP-2 subunit µ2 blocks the Arc-mediated reduction in mEPSC amplitude, effect that is restored by re-introducing µ2. The Arc/AP-2 interaction plays an important role in homeostatic synaptic scaling as the Arc-dependent decrease in mEPSC amplitude, induced by a chronic increase in neuronal activity, is inhibited by AP-2 depletion. This data provides a mechanism to explain how activity-dependent expression of Arc decisively controls the fate of AMPAR at the cell surface and modulates synaptic strength, via the direct interaction with the endocytic clathrin adaptor AP-2.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QP Physiology | ||||||||
| Divisions: | Faculty of Science > Life Sciences (2010- ) Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Neural transmission -- Regulation, Endocytosis | ||||||||
| Journal or Publication Title: | eNeuro | ||||||||
| Publisher: | Society for Neuroscience | ||||||||
| ISSN: | 2373-2822 | ||||||||
| Official Date: | 4 May 2016 | ||||||||
| Dates: |
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| Volume: | 3 | ||||||||
| Number: | 3 | ||||||||
| Article Number: | 0144-15.2016 | ||||||||
| DOI: | 10.1523/ENEURO.0144-15.2016 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Research Councils UK (RCUK), GlaxoSmithKline | ||||||||
| Grant number: | BB/J02127X/1 (BBSRC), BB/H018344/1 (BBSRC), 2012/50147-5 (FAPESP), 2009/50650-6 (FAPESP) |
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