Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes
The circadian clock, an internal time-keeping system orchestrates 24 hr rhythms in physiology and behavior by regulating rhythmic transcription in cells. Astrocytes, the most abundant glial cells, play crucial roles in CNS functions, but the impact of the circadian clock on astrocyte functions remai...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2024-11-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/96357 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846141177357664256 |
|---|---|
| author | Ji Eun Ryu Kyu-Won Shim Hyun Woong Roh Minsung Park Jae-Hyung Lee Eun Young Kim |
| author_facet | Ji Eun Ryu Kyu-Won Shim Hyun Woong Roh Minsung Park Jae-Hyung Lee Eun Young Kim |
| author_sort | Ji Eun Ryu |
| collection | DOAJ |
| description | The circadian clock, an internal time-keeping system orchestrates 24 hr rhythms in physiology and behavior by regulating rhythmic transcription in cells. Astrocytes, the most abundant glial cells, play crucial roles in CNS functions, but the impact of the circadian clock on astrocyte functions remains largely unexplored. In this study, we identified 412 circadian rhythmic transcripts in cultured mouse cortical astrocytes through RNA sequencing. Gene Ontology analysis indicated that genes involved in Ca2+ homeostasis are under circadian control. Notably, Herpud1 (Herp) exhibited robust circadian rhythmicity at both mRNA and protein levels, a rhythm disrupted in astrocytes lacking the circadian transcription factor, BMAL1. HERP regulated endoplasmic reticulum (ER) Ca2+ release by modulating the degradation of inositol 1,4,5-trisphosphate receptors (ITPRs). ATP-stimulated ER Ca2+ release varied with the circadian phase, being more pronounced at subjective night phase, likely due to the rhythmic expression of ITPR2. Correspondingly, ATP-stimulated cytosolic Ca2+ increases were heightened at the subjective night phase. This rhythmic ER Ca2+ response led to circadian phase-dependent variations in the phosphorylation of Connexin 43 (Ser368) and gap junctional communication. Given the role of gap junction channel (GJC) in propagating Ca2+ signals, we suggest that this circadian regulation of ER Ca2+ responses could affect astrocytic modulation of synaptic activity according to the time of day. Overall, our study enhances the understanding of how the circadian clock influences astrocyte function in the CNS, shedding light on their potential role in daily variations of brain activity and health. |
| format | Article |
| id | doaj-art-2f587f1ff5344b11b6a0058a0f81bb3f |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-2f587f1ff5344b11b6a0058a0f81bb3f2024-12-04T15:34:16ZengeLife Sciences Publications LtdeLife2050-084X2024-11-011310.7554/eLife.96357Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytesJi Eun Ryu0https://orcid.org/0009-0000-1438-5018Kyu-Won Shim1Hyun Woong Roh2Minsung Park3Jae-Hyung Lee4https://orcid.org/0000-0002-5085-6988Eun Young Kim5https://orcid.org/0000-0001-6466-8622Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea; Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of KoreaInterdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of KoreaNeuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea; Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of KoreaNeuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea; Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of KoreaDepartment of Oral Microbiology, College of Dentistry, Kyung Hee University, Seoul, Republic of KoreaNeuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea; Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of KoreaThe circadian clock, an internal time-keeping system orchestrates 24 hr rhythms in physiology and behavior by regulating rhythmic transcription in cells. Astrocytes, the most abundant glial cells, play crucial roles in CNS functions, but the impact of the circadian clock on astrocyte functions remains largely unexplored. In this study, we identified 412 circadian rhythmic transcripts in cultured mouse cortical astrocytes through RNA sequencing. Gene Ontology analysis indicated that genes involved in Ca2+ homeostasis are under circadian control. Notably, Herpud1 (Herp) exhibited robust circadian rhythmicity at both mRNA and protein levels, a rhythm disrupted in astrocytes lacking the circadian transcription factor, BMAL1. HERP regulated endoplasmic reticulum (ER) Ca2+ release by modulating the degradation of inositol 1,4,5-trisphosphate receptors (ITPRs). ATP-stimulated ER Ca2+ release varied with the circadian phase, being more pronounced at subjective night phase, likely due to the rhythmic expression of ITPR2. Correspondingly, ATP-stimulated cytosolic Ca2+ increases were heightened at the subjective night phase. This rhythmic ER Ca2+ response led to circadian phase-dependent variations in the phosphorylation of Connexin 43 (Ser368) and gap junctional communication. Given the role of gap junction channel (GJC) in propagating Ca2+ signals, we suggest that this circadian regulation of ER Ca2+ responses could affect astrocytic modulation of synaptic activity according to the time of day. Overall, our study enhances the understanding of how the circadian clock influences astrocyte function in the CNS, shedding light on their potential role in daily variations of brain activity and health.https://elifesciences.org/articles/96357astrocytescircadiangap junctionsCa2+Herpud1endoplasmic reticulum |
| spellingShingle | Ji Eun Ryu Kyu-Won Shim Hyun Woong Roh Minsung Park Jae-Hyung Lee Eun Young Kim Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes eLife astrocytes circadian gap junctions Ca2+ Herpud1 endoplasmic reticulum |
| title | Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes |
| title_full | Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes |
| title_fullStr | Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes |
| title_full_unstemmed | Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes |
| title_short | Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes |
| title_sort | circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes |
| topic | astrocytes circadian gap junctions Ca2+ Herpud1 endoplasmic reticulum |
| url | https://elifesciences.org/articles/96357 |
| work_keys_str_mv | AT jieunryu circadianregulationofendoplasmicreticulumcalciumresponseinculturedmouseastrocytes AT kyuwonshim circadianregulationofendoplasmicreticulumcalciumresponseinculturedmouseastrocytes AT hyunwoongroh circadianregulationofendoplasmicreticulumcalciumresponseinculturedmouseastrocytes AT minsungpark circadianregulationofendoplasmicreticulumcalciumresponseinculturedmouseastrocytes AT jaehyunglee circadianregulationofendoplasmicreticulumcalciumresponseinculturedmouseastrocytes AT eunyoungkim circadianregulationofendoplasmicreticulumcalciumresponseinculturedmouseastrocytes |