Glial Ca2+signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability
Glial-neuronal signaling at synapses is widely studied, but how glia interact with neuronal somas to regulate their activity is unclear. Drosophila cortex glia are restricted to brain regions devoid of synapses, providing an opportunity to characterize interactions with neuronal somas. Mutations in...
| Principais autores: | , , , , |
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| Outros Autores: | |
| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
eLife Sciences Publications, Ltd
2020
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| Acesso em linha: | https://hdl.handle.net/1721.1/125501 |
| _version_ | 1826190629974048768 |
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| author | Weiss Sharabi, Shirley Melom, Jan Elizabeth Ormerod, Kiel G Zhang, Yao Littleton, J. Troy |
| author2 | Picower Institute for Learning and Memory |
| author_facet | Picower Institute for Learning and Memory Weiss Sharabi, Shirley Melom, Jan Elizabeth Ormerod, Kiel G Zhang, Yao Littleton, J. Troy |
| author_sort | Weiss Sharabi, Shirley |
| collection | MIT |
| description | Glial-neuronal signaling at synapses is widely studied, but how glia interact with neuronal somas to regulate their activity is unclear. Drosophila cortex glia are restricted to brain regions devoid of synapses, providing an opportunity to characterize interactions with neuronal somas. Mutations in the cortex glial NCKXzydecoelevate basal Ca2+, predisposing animals to seizure-like behavior. To determine how cortex glial Ca2+signaling controls neuronal excitability, we performed an in vivo modifier screen of the NCKXzydecoseizure phenotype. We show that elevation of glial Ca2+causes hyperactivation of calcineurin-dependent endocytosis and accumulation of early endosomes. Knockdown of sandman, a K2P channel, recapitulates NCKXzydecoseizures. Indeed, sandman expression on cortex glial membranes is substantially reduced in NCKXzydecomutants, indicating enhanced internalization of sandman predisposes animals to seizures. These data provide an unexpected link between glial Ca2+signaling and the well-known role of glia in K+buffering as a key mechanism for regulating neuronal excitability. |
| first_indexed | 2024-09-23T08:43:15Z |
| format | Article |
| id | mit-1721.1/125501 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:43:15Z |
| publishDate | 2020 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| spelling | mit-1721.1/1255012022-09-23T14:05:47Z Glial Ca2+signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability Weiss Sharabi, Shirley Melom, Jan Elizabeth Ormerod, Kiel G Zhang, Yao Littleton, J. Troy Picower Institute for Learning and Memory Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Glial-neuronal signaling at synapses is widely studied, but how glia interact with neuronal somas to regulate their activity is unclear. Drosophila cortex glia are restricted to brain regions devoid of synapses, providing an opportunity to characterize interactions with neuronal somas. Mutations in the cortex glial NCKXzydecoelevate basal Ca2+, predisposing animals to seizure-like behavior. To determine how cortex glial Ca2+signaling controls neuronal excitability, we performed an in vivo modifier screen of the NCKXzydecoseizure phenotype. We show that elevation of glial Ca2+causes hyperactivation of calcineurin-dependent endocytosis and accumulation of early endosomes. Knockdown of sandman, a K2P channel, recapitulates NCKXzydecoseizures. Indeed, sandman expression on cortex glial membranes is substantially reduced in NCKXzydecomutants, indicating enhanced internalization of sandman predisposes animals to seizures. These data provide an unexpected link between glial Ca2+signaling and the well-known role of glia in K+buffering as a key mechanism for regulating neuronal excitability. National Institutes of Health (U.S.) (Grant NS40296) National Institutes of Health (U.S.) (Grant MH104536) National Institutes of Health (U.S.) (Grant P40OD018537) 2020-05-27T15:39:39Z 2020-05-27T15:39:39Z 2019-04 2020-01-15T18:05:00Z Article http://purl.org/eprint/type/JournalArticle 1534-4983 https://hdl.handle.net/1721.1/125501 Weiss, Shirley et al. “Glial Ca2+signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability.” eLife 8 (2019): e44186 © 2019 The Author(s) en https://dx.doi.org/10.7554/ELIFE.44186 eLife Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd eLife |
| spellingShingle | Weiss Sharabi, Shirley Melom, Jan Elizabeth Ormerod, Kiel G Zhang, Yao Littleton, J. Troy Glial Ca2+signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability |
| title | Glial Ca2+signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability |
| title_full | Glial Ca2+signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability |
| title_fullStr | Glial Ca2+signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability |
| title_full_unstemmed | Glial Ca2+signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability |
| title_short | Glial Ca2+signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability |
| title_sort | glial ca2 signaling links endocytosis to k buffering around neuronal somas to regulate excitability |
| url | https://hdl.handle.net/1721.1/125501 |
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