A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing development
Metazoans have evolved various quality control mechanisms to cope with cellular stress inflicted by external and physiological conditions. ATF4 is a major effector of the integrated stress response, an evolutionarily conserved pathway that mediates adaptation to various cellular stressors. Loss of f...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2022-03-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/15/3/dmm049119 |
| _version_ | 1828792020998553600 |
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| author | Deepika Vasudevan Hidetaka Katow Huai-Wei Huang Grace Tang Hyung Don Ryoo |
| author_facet | Deepika Vasudevan Hidetaka Katow Huai-Wei Huang Grace Tang Hyung Don Ryoo |
| author_sort | Deepika Vasudevan |
| collection | DOAJ |
| description | Metazoans have evolved various quality control mechanisms to cope with cellular stress inflicted by external and physiological conditions. ATF4 is a major effector of the integrated stress response, an evolutionarily conserved pathway that mediates adaptation to various cellular stressors. Loss of function of Drosophila ATF4, encoded by the gene cryptocephal (crc), results in lethality during pupal development. The roles of crc in Drosophila disease models and in adult tissue homeostasis thus remain poorly understood. Here, we report that a protein-trap Minos-mediated integration cassette insertion in the crc locus generates a Crc-GFP fusion protein that allows visualization of Crc activity in vivo. This allele also acts as a hypomorphic mutant that uncovers previously unknown roles for crc. Specifically, the crc protein-trap line shows Crc-GFP induction in a Drosophila model for retinitis pigmentosa. This crc allele renders flies more vulnerable to amino acid deprivation and age-dependent retinal degeneration. These mutants also show defects in wing veins and oocyte maturation. Together, our data reveal previously unknown roles for crc in development, cellular homeostasis and photoreceptor survival. This article has an associated First Person interview with the first author of the paper. |
| first_indexed | 2024-12-12T03:01:03Z |
| format | Article |
| id | doaj.art-1bf2f8d073814d7eb9b706e8fa5b2e07 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-12T03:01:03Z |
| publishDate | 2022-03-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-1bf2f8d073814d7eb9b706e8fa5b2e072022-12-22T00:40:37ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112022-03-0115310.1242/dmm.049119049119A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing developmentDeepika Vasudevan0Hidetaka Katow1Huai-Wei Huang2Grace Tang3Hyung Don Ryoo4 Department of Cell Biology, New York University Grossman School of Medicine, New York, NY 10016, USA Department of Cell Biology, New York University Grossman School of Medicine, New York, NY 10016, USA Department of Cell Biology, New York University Grossman School of Medicine, New York, NY 10016, USA Department of Cell Biology, New York University Grossman School of Medicine, New York, NY 10016, USA Department of Cell Biology, New York University Grossman School of Medicine, New York, NY 10016, USA Metazoans have evolved various quality control mechanisms to cope with cellular stress inflicted by external and physiological conditions. ATF4 is a major effector of the integrated stress response, an evolutionarily conserved pathway that mediates adaptation to various cellular stressors. Loss of function of Drosophila ATF4, encoded by the gene cryptocephal (crc), results in lethality during pupal development. The roles of crc in Drosophila disease models and in adult tissue homeostasis thus remain poorly understood. Here, we report that a protein-trap Minos-mediated integration cassette insertion in the crc locus generates a Crc-GFP fusion protein that allows visualization of Crc activity in vivo. This allele also acts as a hypomorphic mutant that uncovers previously unknown roles for crc. Specifically, the crc protein-trap line shows Crc-GFP induction in a Drosophila model for retinitis pigmentosa. This crc allele renders flies more vulnerable to amino acid deprivation and age-dependent retinal degeneration. These mutants also show defects in wing veins and oocyte maturation. Together, our data reveal previously unknown roles for crc in development, cellular homeostasis and photoreceptor survival. This article has an associated First Person interview with the first author of the paper.http://dmm.biologists.org/content/15/3/dmm049119atf4crcer stressintegrated stress responseretinitis pigmentosaadrpretinal degeneration |
| spellingShingle | Deepika Vasudevan Hidetaka Katow Huai-Wei Huang Grace Tang Hyung Don Ryoo A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing development Disease Models & Mechanisms atf4 crc er stress integrated stress response retinitis pigmentosa adrp retinal degeneration |
| title | A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing development |
| title_full | A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing development |
| title_fullStr | A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing development |
| title_full_unstemmed | A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing development |
| title_short | A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing development |
| title_sort | protein trap allele reveals roles for drosophila atf4 in photoreceptor degeneration oogenesis and wing development |
| topic | atf4 crc er stress integrated stress response retinitis pigmentosa adrp retinal degeneration |
| url | http://dmm.biologists.org/content/15/3/dmm049119 |
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