Exploring Excitotoxicity and Regulation of a Constitutively Active TRP Ca2+ Channel in Drosophila
Unregulated Ca2+ influx affects intracellular Ca2+ homoeostasis, which may lead to neuronal death. In Drosophila, following the activation of rhodopsin the TRP Ca2+ channel is open to mediate the light-dependent depolarization. A constitutively active TRP channel triggers the degeneration of TrpP365...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Fly |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/19336934.2020.1851586 |
| _version_ | 1827810961137860608 |
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| author | Bih-Hwa Shieh Lucinda Nuzum Inga Kristaponyte |
| author_facet | Bih-Hwa Shieh Lucinda Nuzum Inga Kristaponyte |
| author_sort | Bih-Hwa Shieh |
| collection | DOAJ |
| description | Unregulated Ca2+ influx affects intracellular Ca2+ homoeostasis, which may lead to neuronal death. In Drosophila, following the activation of rhodopsin the TRP Ca2+ channel is open to mediate the light-dependent depolarization. A constitutively active TRP channel triggers the degeneration of TrpP365/+ photoreceptors. To explore retinal degeneration, we employed a multidisciplinary approach including live imaging using GFP tagged actin and arrestin 2. Importantly, we demonstrate that the major rhodopsin (Rh1) was greatly reduced before the onset of rhabdomere degeneration; a great reduction of Rh1 affects the maintenance of rhabdomere leading to degeneration of photoreceptors. TrpP365/+ also led to the up-regulation of CaMKII, which is beneficial as suppression of CaMKII accelerated retinal degeneration. We explored the regulation of TRP by investigating the genetic interaction between TrpP365/+ and mutants affecting the turnover of diacylglycerol (DAG). We show a loss of phospholipase C in norpAP24 exhibited a great reduction of the DAG content delayed degeneration of TrpP365/+ photoreceptors. In contrast, knockdown or mutations in DAG lipase (InaE) that is accompanied by slightly reduced levels of most DAG but an increased level of DAG 34:1, exacerbated retinal degeneration of TrpP365/+. Together, our findings support the notion that DAG plays a role in regulating TRP. Interestingly, DAG lipase is likely required during photoreceptor development as TrpP365/+; inaEN125 double mutants contained severely degenerated rhabdomeres. |
| first_indexed | 2024-03-11T22:58:45Z |
| format | Article |
| id | doaj.art-8ccc208d52f84b3f9821e65d3c5c038e |
| institution | Directory Open Access Journal |
| issn | 1933-6934 1933-6942 |
| language | English |
| last_indexed | 2024-03-11T22:58:45Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Fly |
| spelling | doaj.art-8ccc208d52f84b3f9821e65d3c5c038e2023-09-21T15:09:08ZengTaylor & Francis GroupFly1933-69341933-69422021-01-0115182710.1080/19336934.2020.18515861851586Exploring Excitotoxicity and Regulation of a Constitutively Active TRP Ca2+ Channel in DrosophilaBih-Hwa Shieh0Lucinda Nuzum1Inga Kristaponyte2Center for Molecular Neuroscience and Vanderbilt Vision Research Center, Vanderbilt UniversityCenter for Molecular Neuroscience and Vanderbilt Vision Research Center, Vanderbilt UniversityCenter for Molecular Neuroscience and Vanderbilt Vision Research Center, Vanderbilt UniversityUnregulated Ca2+ influx affects intracellular Ca2+ homoeostasis, which may lead to neuronal death. In Drosophila, following the activation of rhodopsin the TRP Ca2+ channel is open to mediate the light-dependent depolarization. A constitutively active TRP channel triggers the degeneration of TrpP365/+ photoreceptors. To explore retinal degeneration, we employed a multidisciplinary approach including live imaging using GFP tagged actin and arrestin 2. Importantly, we demonstrate that the major rhodopsin (Rh1) was greatly reduced before the onset of rhabdomere degeneration; a great reduction of Rh1 affects the maintenance of rhabdomere leading to degeneration of photoreceptors. TrpP365/+ also led to the up-regulation of CaMKII, which is beneficial as suppression of CaMKII accelerated retinal degeneration. We explored the regulation of TRP by investigating the genetic interaction between TrpP365/+ and mutants affecting the turnover of diacylglycerol (DAG). We show a loss of phospholipase C in norpAP24 exhibited a great reduction of the DAG content delayed degeneration of TrpP365/+ photoreceptors. In contrast, knockdown or mutations in DAG lipase (InaE) that is accompanied by slightly reduced levels of most DAG but an increased level of DAG 34:1, exacerbated retinal degeneration of TrpP365/+. Together, our findings support the notion that DAG plays a role in regulating TRP. Interestingly, DAG lipase is likely required during photoreceptor development as TrpP365/+; inaEN125 double mutants contained severely degenerated rhabdomeres.http://dx.doi.org/10.1080/19336934.2020.1851586trprhodopsintrplcamkiidag lipaseinaenorpadag |
| spellingShingle | Bih-Hwa Shieh Lucinda Nuzum Inga Kristaponyte Exploring Excitotoxicity and Regulation of a Constitutively Active TRP Ca2+ Channel in Drosophila Fly trp rhodopsin trpl camkii dag lipase inae norpa dag |
| title | Exploring Excitotoxicity and Regulation of a Constitutively Active TRP Ca2+ Channel in Drosophila |
| title_full | Exploring Excitotoxicity and Regulation of a Constitutively Active TRP Ca2+ Channel in Drosophila |
| title_fullStr | Exploring Excitotoxicity and Regulation of a Constitutively Active TRP Ca2+ Channel in Drosophila |
| title_full_unstemmed | Exploring Excitotoxicity and Regulation of a Constitutively Active TRP Ca2+ Channel in Drosophila |
| title_short | Exploring Excitotoxicity and Regulation of a Constitutively Active TRP Ca2+ Channel in Drosophila |
| title_sort | exploring excitotoxicity and regulation of a constitutively active trp ca2 channel in drosophila |
| topic | trp rhodopsin trpl camkii dag lipase inae norpa dag |
| url | http://dx.doi.org/10.1080/19336934.2020.1851586 |
| work_keys_str_mv | AT bihhwashieh exploringexcitotoxicityandregulationofaconstitutivelyactivetrpca2channelindrosophila AT lucindanuzum exploringexcitotoxicityandregulationofaconstitutivelyactivetrpca2channelindrosophila AT ingakristaponyte exploringexcitotoxicityandregulationofaconstitutivelyactivetrpca2channelindrosophila |