The physiological role of Homer2a and its novel short isoform, Homer2e, in NMDA receptor-mediated apoptosis in cerebellar granule cells
Abstract Homer is a postsynaptic scaffold protein, which has long and short isoforms. The long form of Homer consists of an N-terminal target-binding domain and a C-terminal multimerization domain, linking multiple proteins within a complex. The short form of Homer only has the N-terminal domain and...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Molecular Brain |
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| Online Access: | https://doi.org/10.1186/s13041-021-00804-8 |
| _version_ | 1819100759942234112 |
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| author | Teiichi Furuichi Yuko Muto Tetsushi Sadakata Yumi Sato Kanehiro Hayashi Yoko Shiraishi-Yamaguchi Yo Shinoda |
| author_facet | Teiichi Furuichi Yuko Muto Tetsushi Sadakata Yumi Sato Kanehiro Hayashi Yoko Shiraishi-Yamaguchi Yo Shinoda |
| author_sort | Teiichi Furuichi |
| collection | DOAJ |
| description | Abstract Homer is a postsynaptic scaffold protein, which has long and short isoforms. The long form of Homer consists of an N-terminal target-binding domain and a C-terminal multimerization domain, linking multiple proteins within a complex. The short form of Homer only has the N-terminal domain and likely acts as a dominant negative regulator. Homer2a, one of the long form isoforms of the Homer family, expresses with a transient peak in the early postnatal stage of mouse cerebellar granule cells (CGCs); however, the functions of Homer2a in CGCs are not fully understood yet. In this study, we investigated the physiological roles of Homer2a in CGCs using recombinant adenovirus vectors. Overexpression of the Homer2a N-terminal domain construct, which was made structurally reminiscent with Homer1a, altered NMDAR1 localization, decreased NMDA currents, and promoted the survival of CGCs. These results suggest that the Homer2a N-terminal domain acts as a dominant negative protein to attenuate NMDAR-mediated excitotoxicity. Moreover, we identified a novel short form N-terminal domain-containing Homer2, named Homer2e, which was induced by apoptotic stimulation such as ischemic brain injury. Our study suggests that the long and short forms of Homer2 are involved in apoptosis of CGCs. |
| first_indexed | 2024-12-22T01:07:53Z |
| format | Article |
| id | doaj.art-a014e7707968454d9be2cf9f537d2798 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-22T01:07:53Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-a014e7707968454d9be2cf9f537d27982022-12-21T18:44:02ZengBMCMolecular Brain1756-66062021-06-0114111110.1186/s13041-021-00804-8The physiological role of Homer2a and its novel short isoform, Homer2e, in NMDA receptor-mediated apoptosis in cerebellar granule cellsTeiichi Furuichi0Yuko Muto1Tetsushi Sadakata2Yumi Sato3Kanehiro Hayashi4Yoko Shiraishi-Yamaguchi5Yo Shinoda6Laboratory for Molecular Neurogenesis, RIKEN Brain Science InstituteLaboratory for Molecular Neurogenesis, RIKEN Brain Science InstituteLaboratory for Molecular Neurogenesis, RIKEN Brain Science InstituteLaboratory for Molecular Neurogenesis, RIKEN Brain Science InstituteLaboratory for Molecular Neurogenesis, RIKEN Brain Science InstituteLaboratory for Molecular Neurogenesis, RIKEN Brain Science InstituteLaboratory for Molecular Neurogenesis, RIKEN Brain Science InstituteAbstract Homer is a postsynaptic scaffold protein, which has long and short isoforms. The long form of Homer consists of an N-terminal target-binding domain and a C-terminal multimerization domain, linking multiple proteins within a complex. The short form of Homer only has the N-terminal domain and likely acts as a dominant negative regulator. Homer2a, one of the long form isoforms of the Homer family, expresses with a transient peak in the early postnatal stage of mouse cerebellar granule cells (CGCs); however, the functions of Homer2a in CGCs are not fully understood yet. In this study, we investigated the physiological roles of Homer2a in CGCs using recombinant adenovirus vectors. Overexpression of the Homer2a N-terminal domain construct, which was made structurally reminiscent with Homer1a, altered NMDAR1 localization, decreased NMDA currents, and promoted the survival of CGCs. These results suggest that the Homer2a N-terminal domain acts as a dominant negative protein to attenuate NMDAR-mediated excitotoxicity. Moreover, we identified a novel short form N-terminal domain-containing Homer2, named Homer2e, which was induced by apoptotic stimulation such as ischemic brain injury. Our study suggests that the long and short forms of Homer2 are involved in apoptosis of CGCs.https://doi.org/10.1186/s13041-021-00804-8Homer2Cerebellar granule cellNMDARExcitotoxicity |
| spellingShingle | Teiichi Furuichi Yuko Muto Tetsushi Sadakata Yumi Sato Kanehiro Hayashi Yoko Shiraishi-Yamaguchi Yo Shinoda The physiological role of Homer2a and its novel short isoform, Homer2e, in NMDA receptor-mediated apoptosis in cerebellar granule cells Molecular Brain Homer2 Cerebellar granule cell NMDAR Excitotoxicity |
| title | The physiological role of Homer2a and its novel short isoform, Homer2e, in NMDA receptor-mediated apoptosis in cerebellar granule cells |
| title_full | The physiological role of Homer2a and its novel short isoform, Homer2e, in NMDA receptor-mediated apoptosis in cerebellar granule cells |
| title_fullStr | The physiological role of Homer2a and its novel short isoform, Homer2e, in NMDA receptor-mediated apoptosis in cerebellar granule cells |
| title_full_unstemmed | The physiological role of Homer2a and its novel short isoform, Homer2e, in NMDA receptor-mediated apoptosis in cerebellar granule cells |
| title_short | The physiological role of Homer2a and its novel short isoform, Homer2e, in NMDA receptor-mediated apoptosis in cerebellar granule cells |
| title_sort | physiological role of homer2a and its novel short isoform homer2e in nmda receptor mediated apoptosis in cerebellar granule cells |
| topic | Homer2 Cerebellar granule cell NMDAR Excitotoxicity |
| url | https://doi.org/10.1186/s13041-021-00804-8 |
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