Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway
Synaptic scaling is a form of homeostatic plasticity driven by transcription-dependent changes in AMPA-type glutamate receptor (AMPAR) trafficking. To uncover the pathways involved, we performed a cell-type-specific screen for transcripts persistently altered during scaling, which identified the μ s...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/109123 https://orcid.org/0000-0002-2801-8101 |
| _version_ | 1811078274075328512 |
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| author | Steinmetz, Celine C. Tatavarty, Vedakumar Sugino, Ken Shima, Yasuyuki Joseph, Anne Lin, Heather Rutlin, Michael Hempel, Chris M. Okaty, Benjamin W. Paradis, Suzanne Nelson, Sacha B. Turrigiano, Gina G. Lambo, Mary E. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Steinmetz, Celine C. Tatavarty, Vedakumar Sugino, Ken Shima, Yasuyuki Joseph, Anne Lin, Heather Rutlin, Michael Hempel, Chris M. Okaty, Benjamin W. Paradis, Suzanne Nelson, Sacha B. Turrigiano, Gina G. Lambo, Mary E. |
| author_sort | Steinmetz, Celine C. |
| collection | MIT |
| description | Synaptic scaling is a form of homeostatic plasticity driven by transcription-dependent changes in AMPA-type glutamate receptor (AMPAR) trafficking. To uncover the pathways involved, we performed a cell-type-specific screen for transcripts persistently altered during scaling, which identified the μ subunit (μ3A) of the adaptor protein complex AP-3A. Synaptic scaling increased μ3A (but not other AP-3 subunits) in pyramidal neurons and redistributed dendritic μ3A and AMPAR to recycling endosomes (REs). Knockdown of μ3A prevented synaptic scaling and this redistribution, while overexpression (OE) of full-length μ3A or a truncated μ3A that cannot interact with the AP-3A complex was sufficient to drive AMPAR to REs. Finally, OE of μ3A acted synergistically with GRIP1 to recruit AMPAR to the dendritic membrane. These data suggest that excess μ3A acts independently of the AP-3A complex to reroute AMPAR to RE, generating a reservoir of receptors essential for the regulated recruitment to the synaptic membrane during scaling up. |
| first_indexed | 2024-09-23T10:57:04Z |
| format | Article |
| id | mit-1721.1/109123 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:57:04Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1091232022-10-01T00:08:36Z Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway Steinmetz, Celine C. Tatavarty, Vedakumar Sugino, Ken Shima, Yasuyuki Joseph, Anne Lin, Heather Rutlin, Michael Hempel, Chris M. Okaty, Benjamin W. Paradis, Suzanne Nelson, Sacha B. Turrigiano, Gina G. Lambo, Mary E. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Lambo, Mary E. Synaptic scaling is a form of homeostatic plasticity driven by transcription-dependent changes in AMPA-type glutamate receptor (AMPAR) trafficking. To uncover the pathways involved, we performed a cell-type-specific screen for transcripts persistently altered during scaling, which identified the μ subunit (μ3A) of the adaptor protein complex AP-3A. Synaptic scaling increased μ3A (but not other AP-3 subunits) in pyramidal neurons and redistributed dendritic μ3A and AMPAR to recycling endosomes (REs). Knockdown of μ3A prevented synaptic scaling and this redistribution, while overexpression (OE) of full-length μ3A or a truncated μ3A that cannot interact with the AP-3A complex was sufficient to drive AMPAR to REs. Finally, OE of μ3A acted synergistically with GRIP1 to recruit AMPAR to the dendritic membrane. These data suggest that excess μ3A acts independently of the AP-3A complex to reroute AMPAR to RE, generating a reservoir of receptors essential for the regulated recruitment to the synaptic membrane during scaling up. 2017-05-16T18:12:38Z 2017-05-16T18:12:38Z 2016-08 2016-07 Article http://purl.org/eprint/type/JournalArticle 2211-1247 http://hdl.handle.net/1721.1/109123 Steinmetz, Celine C. et al. “Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway.” Cell Reports 16.10 (2016): 2711–2722. https://orcid.org/0000-0002-2801-8101 en_US http://dx.doi.org/10.1016/j.celrep.2016.08.009 Cell Reports Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Steinmetz, Celine C. Tatavarty, Vedakumar Sugino, Ken Shima, Yasuyuki Joseph, Anne Lin, Heather Rutlin, Michael Hempel, Chris M. Okaty, Benjamin W. Paradis, Suzanne Nelson, Sacha B. Turrigiano, Gina G. Lambo, Mary E. Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway |
| title | Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway |
| title_full | Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway |
| title_fullStr | Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway |
| title_full_unstemmed | Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway |
| title_short | Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway |
| title_sort | upregulation of μ3a drives homeostatic plasticity by rerouting ampar into the recycling endosomal pathway |
| url | http://hdl.handle.net/1721.1/109123 https://orcid.org/0000-0002-2801-8101 |
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