iPLA2-VIA is required for healthy aging of neurons, muscle, and the female germline in Drosophila melanogaster.
Neurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the cal...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/fe9e763e7e17403fbc75272083127bfc |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:fe9e763e7e17403fbc75272083127bfc |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:fe9e763e7e17403fbc75272083127bfc2021-12-02T20:14:45ZiPLA2-VIA is required for healthy aging of neurons, muscle, and the female germline in Drosophila melanogaster.1932-620310.1371/journal.pone.0256738https://doaj.org/article/fe9e763e7e17403fbc75272083127bfc2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256738https://doaj.org/toc/1932-6203Neurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A2 (iPLA2) VIA gene CG6718, the Drosophila melanogaster ortholog of human PLA2G6/PARK14, mutations in which cause a suite of NDs collectively called PLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA2-VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA2-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenous iPLA2-VIA mRNA expression in adult germ cells, and transgenic HA-tagged iPLA2-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA2-VIA is critical for mitochondrial integrity in the Drosophila female germline, which may provide a novel context to investigate its functions with parallels to PLAN.Surya Jyoti BanerjeeAdina SchonbrunSogol EizadshenassShimshon BenjiYaakov Tzvi CantorLiam EliachMatthew LubinZev NarroweJeremy PurowBenjamin ShulmanLeib WienerJosefa SteinhauerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0256738 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Surya Jyoti Banerjee Adina Schonbrun Sogol Eizadshenass Shimshon Benji Yaakov Tzvi Cantor Liam Eliach Matthew Lubin Zev Narrowe Jeremy Purow Benjamin Shulman Leib Wiener Josefa Steinhauer iPLA2-VIA is required for healthy aging of neurons, muscle, and the female germline in Drosophila melanogaster. |
| description |
Neurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A2 (iPLA2) VIA gene CG6718, the Drosophila melanogaster ortholog of human PLA2G6/PARK14, mutations in which cause a suite of NDs collectively called PLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA2-VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA2-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenous iPLA2-VIA mRNA expression in adult germ cells, and transgenic HA-tagged iPLA2-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA2-VIA is critical for mitochondrial integrity in the Drosophila female germline, which may provide a novel context to investigate its functions with parallels to PLAN. |
| format |
article |
| author |
Surya Jyoti Banerjee Adina Schonbrun Sogol Eizadshenass Shimshon Benji Yaakov Tzvi Cantor Liam Eliach Matthew Lubin Zev Narrowe Jeremy Purow Benjamin Shulman Leib Wiener Josefa Steinhauer |
| author_facet |
Surya Jyoti Banerjee Adina Schonbrun Sogol Eizadshenass Shimshon Benji Yaakov Tzvi Cantor Liam Eliach Matthew Lubin Zev Narrowe Jeremy Purow Benjamin Shulman Leib Wiener Josefa Steinhauer |
| author_sort |
Surya Jyoti Banerjee |
| title |
iPLA2-VIA is required for healthy aging of neurons, muscle, and the female germline in Drosophila melanogaster. |
| title_short |
iPLA2-VIA is required for healthy aging of neurons, muscle, and the female germline in Drosophila melanogaster. |
| title_full |
iPLA2-VIA is required for healthy aging of neurons, muscle, and the female germline in Drosophila melanogaster. |
| title_fullStr |
iPLA2-VIA is required for healthy aging of neurons, muscle, and the female germline in Drosophila melanogaster. |
| title_full_unstemmed |
iPLA2-VIA is required for healthy aging of neurons, muscle, and the female germline in Drosophila melanogaster. |
| title_sort |
ipla2-via is required for healthy aging of neurons, muscle, and the female germline in drosophila melanogaster. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/fe9e763e7e17403fbc75272083127bfc |
| work_keys_str_mv |
AT suryajyotibanerjee ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT adinaschonbrun ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT sogoleizadshenass ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT shimshonbenji ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT yaakovtzvicantor ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT liameliach ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT matthewlubin ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT zevnarrowe ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT jeremypurow ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT benjaminshulman ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT leibwiener ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster AT josefasteinhauer ipla2viaisrequiredforhealthyagingofneuronsmuscleandthefemalegermlineindrosophilamelanogaster |
| _version_ |
1718374684396879872 |