AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTP
Summary: Ca2+-permeable AMPA-type glutamate receptors (CP-AMPARs) containing GluA1 but lacking GluA2 subunits contribute to multiple forms of synaptic plasticity, including long-term potentiation (LTP), but mechanisms regulating CP-AMPARs are poorly understood. A-kinase anchoring protein (AKAP) 150...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718315456 |
| _version_ | 1818993033572515840 |
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| author | Alicia M. Purkey Kevin M. Woolfrey Kevin C. Crosby Dominik G. Stich Wallace S. Chick Jason Aoto Mark L. Dell’Acqua |
| author_facet | Alicia M. Purkey Kevin M. Woolfrey Kevin C. Crosby Dominik G. Stich Wallace S. Chick Jason Aoto Mark L. Dell’Acqua |
| author_sort | Alicia M. Purkey |
| collection | DOAJ |
| description | Summary: Ca2+-permeable AMPA-type glutamate receptors (CP-AMPARs) containing GluA1 but lacking GluA2 subunits contribute to multiple forms of synaptic plasticity, including long-term potentiation (LTP), but mechanisms regulating CP-AMPARs are poorly understood. A-kinase anchoring protein (AKAP) 150 scaffolds kinases and phosphatases to regulate GluA1 phosphorylation and trafficking, and trafficking of AKAP150 itself is modulated by palmitoylation on two Cys residues. Here, we developed a palmitoylation-deficient knockin mouse to show that AKAP150 palmitoylation regulates CP-AMPAR incorporation at hippocampal synapses. Using biochemical, super-resolution imaging, and electrophysiological approaches, we found that palmitoylation promotes AKAP150 localization to recycling endosomes and the postsynaptic density (PSD) to limit CP-AMPAR basal synaptic incorporation. In addition, we found that AKAP150 palmitoylation is required for LTP induced by weaker stimulation that recruits CP-AMPARs to synapses but not stronger stimulation that recruits GluA2-containing AMPARs. Thus, AKAP150 palmitoylation controls its subcellular localization to maintain proper basal and activity-dependent regulation of synaptic AMPAR subunit composition. : Purkey et al. uncover a requirement for palmitoylation of the postsynaptic scaffold protein AKAP150 in regulating Ca2+-permeable AMPA receptors to control synaptic plasticity. Keywords: LTP, LTD, calcium-permeable AMPA receptor, AKAP, palmityolation, PKA, calcineurin, PSD |
| first_indexed | 2024-12-20T20:35:37Z |
| format | Article |
| id | doaj.art-5cfe45e1aa0144229d4b3260ef3ae995 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T20:35:37Z |
| publishDate | 2018-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5cfe45e1aa0144229d4b3260ef3ae9952022-12-21T19:27:14ZengElsevierCell Reports2211-12472018-10-01254974987.e4AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTPAlicia M. Purkey0Kevin M. Woolfrey1Kevin C. Crosby2Dominik G. Stich3Wallace S. Chick4Jason Aoto5Mark L. Dell’Acqua6Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USAAdvanced Light Microscopy Core, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA; Advanced Light Microscopy Core, University of Colorado School of Medicine, Aurora, CO 80045, USA; Corresponding authorSummary: Ca2+-permeable AMPA-type glutamate receptors (CP-AMPARs) containing GluA1 but lacking GluA2 subunits contribute to multiple forms of synaptic plasticity, including long-term potentiation (LTP), but mechanisms regulating CP-AMPARs are poorly understood. A-kinase anchoring protein (AKAP) 150 scaffolds kinases and phosphatases to regulate GluA1 phosphorylation and trafficking, and trafficking of AKAP150 itself is modulated by palmitoylation on two Cys residues. Here, we developed a palmitoylation-deficient knockin mouse to show that AKAP150 palmitoylation regulates CP-AMPAR incorporation at hippocampal synapses. Using biochemical, super-resolution imaging, and electrophysiological approaches, we found that palmitoylation promotes AKAP150 localization to recycling endosomes and the postsynaptic density (PSD) to limit CP-AMPAR basal synaptic incorporation. In addition, we found that AKAP150 palmitoylation is required for LTP induced by weaker stimulation that recruits CP-AMPARs to synapses but not stronger stimulation that recruits GluA2-containing AMPARs. Thus, AKAP150 palmitoylation controls its subcellular localization to maintain proper basal and activity-dependent regulation of synaptic AMPAR subunit composition. : Purkey et al. uncover a requirement for palmitoylation of the postsynaptic scaffold protein AKAP150 in regulating Ca2+-permeable AMPA receptors to control synaptic plasticity. Keywords: LTP, LTD, calcium-permeable AMPA receptor, AKAP, palmityolation, PKA, calcineurin, PSDhttp://www.sciencedirect.com/science/article/pii/S2211124718315456 |
| spellingShingle | Alicia M. Purkey Kevin M. Woolfrey Kevin C. Crosby Dominik G. Stich Wallace S. Chick Jason Aoto Mark L. Dell’Acqua AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTP Cell Reports |
| title | AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTP |
| title_full | AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTP |
| title_fullStr | AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTP |
| title_full_unstemmed | AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTP |
| title_short | AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTP |
| title_sort | akap150 palmitoylation regulates synaptic incorporation of ca2 permeable ampa receptors to control ltp |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718315456 |
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