A spatiotemporal reconstruction of the C. elegans pharyngeal cuticle reveals a structure rich in phase-separating proteins
How the cuticles of the roughly 4.5 million species of ecdysozoan animals are constructed is not well understood. Here, we systematically mine gene expression datasets to uncover the spatiotemporal blueprint for how the chitin-based pharyngeal cuticle of the nematode Caenorhabditis elegans is built....
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/79396 |
| _version_ | 1811324934113198080 |
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| author | Muntasir Kamal Levon Tokmakjian Jessica Knox Peter Mastrangelo Jingxiu Ji Hao Cai Jakub W Wojciechowski Michael P Hughes Kristóf Takács Xiaoquan Chu Jianfeng Pei Vince Grolmusz Malgorzata Kotulska Julie Deborah Forman-Kay Peter J Roy |
| author_facet | Muntasir Kamal Levon Tokmakjian Jessica Knox Peter Mastrangelo Jingxiu Ji Hao Cai Jakub W Wojciechowski Michael P Hughes Kristóf Takács Xiaoquan Chu Jianfeng Pei Vince Grolmusz Malgorzata Kotulska Julie Deborah Forman-Kay Peter J Roy |
| author_sort | Muntasir Kamal |
| collection | DOAJ |
| description | How the cuticles of the roughly 4.5 million species of ecdysozoan animals are constructed is not well understood. Here, we systematically mine gene expression datasets to uncover the spatiotemporal blueprint for how the chitin-based pharyngeal cuticle of the nematode Caenorhabditis elegans is built. We demonstrate that the blueprint correctly predicts expression patterns and functional relevance to cuticle development. We find that as larvae prepare to molt, catabolic enzymes are upregulated and the genes that encode chitin synthase, chitin cross-linkers, and homologs of amyloid regulators subsequently peak in expression. Forty-eight percent of the gene products secreted during the molt are predicted to be intrinsically disordered proteins (IDPs), many of which belong to four distinct families whose transcripts are expressed in overlapping waves. These include the IDPAs, IDPBs, and IDPCs, which are introduced for the first time here. All four families have sequence properties that drive phase separation and we demonstrate phase separation for one exemplar in vitro. This systematic analysis represents the first blueprint for cuticle construction and highlights the massive contribution that phase-separating materials make to the structure. |
| first_indexed | 2024-04-13T14:24:04Z |
| format | Article |
| id | doaj.art-7f96998fa7ed4879838769df2846b158 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-13T14:24:04Z |
| publishDate | 2022-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7f96998fa7ed4879838769df2846b1582022-12-22T02:43:23ZengeLife Sciences Publications LtdeLife2050-084X2022-10-011110.7554/eLife.79396A spatiotemporal reconstruction of the C. elegans pharyngeal cuticle reveals a structure rich in phase-separating proteinsMuntasir Kamal0Levon Tokmakjian1Jessica Knox2https://orcid.org/0000-0003-1465-5852Peter Mastrangelo3Jingxiu Ji4https://orcid.org/0000-0003-4121-7719Hao Cai5Jakub W Wojciechowski6https://orcid.org/0000-0001-5289-653XMichael P Hughes7Kristóf Takács8Xiaoquan Chu9Jianfeng Pei10Vince Grolmusz11https://orcid.org/0000-0001-9456-8876Malgorzata Kotulska12https://orcid.org/0000-0002-2015-5339Julie Deborah Forman-Kay13https://orcid.org/0000-0001-8265-972XPeter J Roy14https://orcid.org/0000-0003-2959-2276Department of Molecular Genetics, University of Toronto, Toronto, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, CanadaThe Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, CanadaMolecular Medicine Program, The Hospital for Sick Children, Toronto, CanadaWroclaw University of Science and Technology, Faculty of Fundamental Problems of Technology, Department of Biomedical Engineering, Wroclaw, PolandDepartment of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, United StatesPIT Bioinformatics Group, Institute of Mathematics, Eötvös University, Budapest, HungaryCenter for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, ChinaDepartment of Computer Science and Technology, Tsinghua University, Beijing, ChinaPIT Bioinformatics Group, Institute of Mathematics, Eötvös University, Budapest, HungaryWroclaw University of Science and Technology, Faculty of Fundamental Problems of Technology, Department of Biomedical Engineering, Wroclaw, PolandMolecular Medicine Program, The Hospital for Sick Children, Toronto, Canada; Department of Biochemistry, University of Toronto, Toronto, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, Canada; The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, CanadaHow the cuticles of the roughly 4.5 million species of ecdysozoan animals are constructed is not well understood. Here, we systematically mine gene expression datasets to uncover the spatiotemporal blueprint for how the chitin-based pharyngeal cuticle of the nematode Caenorhabditis elegans is built. We demonstrate that the blueprint correctly predicts expression patterns and functional relevance to cuticle development. We find that as larvae prepare to molt, catabolic enzymes are upregulated and the genes that encode chitin synthase, chitin cross-linkers, and homologs of amyloid regulators subsequently peak in expression. Forty-eight percent of the gene products secreted during the molt are predicted to be intrinsically disordered proteins (IDPs), many of which belong to four distinct families whose transcripts are expressed in overlapping waves. These include the IDPAs, IDPBs, and IDPCs, which are introduced for the first time here. All four families have sequence properties that drive phase separation and we demonstrate phase separation for one exemplar in vitro. This systematic analysis represents the first blueprint for cuticle construction and highlights the massive contribution that phase-separating materials make to the structure.https://elifesciences.org/articles/79396cuticleintrinsically disordered proteinsmoltingsystems analysesphase separationnovel gene families |
| spellingShingle | Muntasir Kamal Levon Tokmakjian Jessica Knox Peter Mastrangelo Jingxiu Ji Hao Cai Jakub W Wojciechowski Michael P Hughes Kristóf Takács Xiaoquan Chu Jianfeng Pei Vince Grolmusz Malgorzata Kotulska Julie Deborah Forman-Kay Peter J Roy A spatiotemporal reconstruction of the C. elegans pharyngeal cuticle reveals a structure rich in phase-separating proteins eLife cuticle intrinsically disordered proteins molting systems analyses phase separation novel gene families |
| title | A spatiotemporal reconstruction of the C. elegans pharyngeal cuticle reveals a structure rich in phase-separating proteins |
| title_full | A spatiotemporal reconstruction of the C. elegans pharyngeal cuticle reveals a structure rich in phase-separating proteins |
| title_fullStr | A spatiotemporal reconstruction of the C. elegans pharyngeal cuticle reveals a structure rich in phase-separating proteins |
| title_full_unstemmed | A spatiotemporal reconstruction of the C. elegans pharyngeal cuticle reveals a structure rich in phase-separating proteins |
| title_short | A spatiotemporal reconstruction of the C. elegans pharyngeal cuticle reveals a structure rich in phase-separating proteins |
| title_sort | spatiotemporal reconstruction of the c elegans pharyngeal cuticle reveals a structure rich in phase separating proteins |
| topic | cuticle intrinsically disordered proteins molting systems analyses phase separation novel gene families |
| url | https://elifesciences.org/articles/79396 |
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