Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior
Autism spectrum disorders (ASDs) are associated with mutations affecting synaptic components, including GluN2B-NMDA receptors (NMDARs) and neurobeachin (NBEA). NBEA participates in biosynthetic pathways to regulate synapse receptor targeting, synaptic function, cognition, and social behavior. Howeve...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718307125 |
| _version_ | 1811331176217968640 |
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| author | Kira V. Gromova Mary Muhia Nicola Rothammer Christine E. Gee Edda Thies Irina Schaefer Sabrina Kress Manfred W. Kilimann Olga Shevchuk Thomas G. Oertner Matthias Kneussel |
| author_facet | Kira V. Gromova Mary Muhia Nicola Rothammer Christine E. Gee Edda Thies Irina Schaefer Sabrina Kress Manfred W. Kilimann Olga Shevchuk Thomas G. Oertner Matthias Kneussel |
| author_sort | Kira V. Gromova |
| collection | DOAJ |
| description | Autism spectrum disorders (ASDs) are associated with mutations affecting synaptic components, including GluN2B-NMDA receptors (NMDARs) and neurobeachin (NBEA). NBEA participates in biosynthetic pathways to regulate synapse receptor targeting, synaptic function, cognition, and social behavior. However, the role of NBEA-mediated transport in specific trafficking routes is unclear. Here, we highlight an additional function for NBEA in the local delivery and surface re-insertion of synaptic receptors in mouse neurons. NBEA dynamically interacts with Rab4-positive recycling endosomes, transiently enters spines in an activity-dependent manner, and regulates GluN2B-NMDAR recycling. Furthermore, we show that the microtubule growth inhibitor kinesin KIF21B constrains NBEA dynamics and is present in the NBEA-recycling endosome-NMDAR complex. Notably, Kif21b knockout decreases NMDAR surface expression and alters social behavior in mice, consistent with reported social deficits in Nbea mutants. The influence of NBEA-KIF21B interactions on GluN2B-NMDAR local recycling may be relevant to mechanisms underlying ASD etiology. |
| first_indexed | 2024-04-13T16:16:36Z |
| format | Article |
| id | doaj.art-ca348ec380c54b27b6fa8ba02855ace0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T16:16:36Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ca348ec380c54b27b6fa8ba02855ace02022-12-22T02:40:04ZengElsevierCell Reports2211-12472018-05-012392705271710.1016/j.celrep.2018.04.112Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social BehaviorKira V. Gromova0Mary Muhia1Nicola Rothammer2Christine E. Gee3Edda Thies4Irina Schaefer5Sabrina Kress6Manfred W. Kilimann7Olga Shevchuk8Thomas G. Oertner9Matthias Kneussel10Department of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Synaptic Physiology, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Molecular Neurobiology, Max-Planck Institute for Experimental Medicine, Göttingen, GermanyCellular Proteomics Research Group, Helmholtz Centre for Infection Research (HZI), Braunschweig, GermanyDepartment of Synaptic Physiology, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyAutism spectrum disorders (ASDs) are associated with mutations affecting synaptic components, including GluN2B-NMDA receptors (NMDARs) and neurobeachin (NBEA). NBEA participates in biosynthetic pathways to regulate synapse receptor targeting, synaptic function, cognition, and social behavior. However, the role of NBEA-mediated transport in specific trafficking routes is unclear. Here, we highlight an additional function for NBEA in the local delivery and surface re-insertion of synaptic receptors in mouse neurons. NBEA dynamically interacts with Rab4-positive recycling endosomes, transiently enters spines in an activity-dependent manner, and regulates GluN2B-NMDAR recycling. Furthermore, we show that the microtubule growth inhibitor kinesin KIF21B constrains NBEA dynamics and is present in the NBEA-recycling endosome-NMDAR complex. Notably, Kif21b knockout decreases NMDAR surface expression and alters social behavior in mice, consistent with reported social deficits in Nbea mutants. The influence of NBEA-KIF21B interactions on GluN2B-NMDAR local recycling may be relevant to mechanisms underlying ASD etiology.http://www.sciencedirect.com/science/article/pii/S2211124718307125autism spectrum disordersynapseneurobeachinNMDA receptorendosomal recyclingRab GTPaseKIF21Bdyneinretromersocial behavior |
| spellingShingle | Kira V. Gromova Mary Muhia Nicola Rothammer Christine E. Gee Edda Thies Irina Schaefer Sabrina Kress Manfred W. Kilimann Olga Shevchuk Thomas G. Oertner Matthias Kneussel Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior Cell Reports autism spectrum disorder synapse neurobeachin NMDA receptor endosomal recycling Rab GTPase KIF21B dynein retromer social behavior |
| title | Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior |
| title_full | Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior |
| title_fullStr | Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior |
| title_full_unstemmed | Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior |
| title_short | Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior |
| title_sort | neurobeachin and the kinesin kif21b are critical for endocytic recycling of nmda receptors and regulate social behavior |
| topic | autism spectrum disorder synapse neurobeachin NMDA receptor endosomal recycling Rab GTPase KIF21B dynein retromer social behavior |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718307125 |
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