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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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716310555 |
| _version_ | 1819168728042962944 |
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| author | Celine C. Steinmetz Vedakumar Tatavarty Ken Sugino Yasuyuki Shima Anne Joseph Heather Lin Michael Rutlin Mary Lambo Chris M. Hempel Benjamin W. Okaty Suzanne Paradis Sacha B. Nelson Gina G. Turrigiano |
| author_facet | Celine C. Steinmetz Vedakumar Tatavarty Ken Sugino Yasuyuki Shima Anne Joseph Heather Lin Michael Rutlin Mary Lambo Chris M. Hempel Benjamin W. Okaty Suzanne Paradis Sacha B. Nelson Gina G. Turrigiano |
| author_sort | Celine C. Steinmetz |
| collection | DOAJ |
| 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 | 2024-12-22T19:08:13Z |
| format | Article |
| id | doaj.art-55bfbd81248d4911acc2ebf4bf9c306d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T19:08:13Z |
| publishDate | 2016-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-55bfbd81248d4911acc2ebf4bf9c306d2022-12-21T18:15:45ZengElsevierCell Reports2211-12472016-09-0116102711272210.1016/j.celrep.2016.08.009Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal PathwayCeline C. Steinmetz0Vedakumar Tatavarty1Ken Sugino2Yasuyuki Shima3Anne Joseph4Heather Lin5Michael Rutlin6Mary Lambo7Chris M. Hempel8Benjamin W. Okaty9Suzanne Paradis10Sacha B. Nelson11Gina G. Turrigiano12Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Brain and Cognitive Science, MIT, Cambridge, MA 02139, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USADepartment of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USASynaptic 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.http://www.sciencedirect.com/science/article/pii/S2211124716310555 |
| spellingShingle | Celine C. Steinmetz Vedakumar Tatavarty Ken Sugino Yasuyuki Shima Anne Joseph Heather Lin Michael Rutlin Mary Lambo Chris M. Hempel Benjamin W. Okaty Suzanne Paradis Sacha B. Nelson Gina G. Turrigiano Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway Cell Reports |
| 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://www.sciencedirect.com/science/article/pii/S2211124716310555 |
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