A C. elegans Zona Pellucida domain protein functions via its ZPc domain
Zona Pellucida domain (ZP) proteins are critical components of the body's external-most protective layers, apical extracellular matrices (aECMs). Although their loss or dysfunction is associated with many diseases, it remains unclear how ZP proteins assemble in aECMs. Current models suggest tha...
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| creator | Cohen, Jennifer D Bermudez, Jessica G Good, Matthew C Sundaram, Meera V |
| description | Zona Pellucida domain (ZP) proteins are critical components of the body's external-most protective layers, apical extracellular matrices (aECMs). Although their loss or dysfunction is associated with many diseases, it remains unclear how ZP proteins assemble in aECMs. Current models suggest that ZP proteins polymerize via their ZPn subdomains, while ZPc subdomains modulate ZPn behavior. Using the model organism C. elegans, we investigated the aECM assembly of one ZP protein, LET-653, which shapes several tubes. Contrary to prevailing models, we find that LET-653 localizes and functions via its ZPc domain. Furthermore, we show that ZPc domain function requires cleavage at the LET-653 C-terminus, likely in part to relieve inhibition of the ZPc by the ZPn domain, but also to promote some other aspect of ZPc domain function. In vitro, the ZPc, but not ZPn, domain bound crystalline aggregates. These data offer a new model for ZP function whereby the ZPc domain is primarily responsible for matrix incorporation and tissue shaping. |
| doi_str_mv | 10.1371/journal.pgen.1009188 |
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Although their loss or dysfunction is associated with many diseases, it remains unclear how ZP proteins assemble in aECMs. Current models suggest that ZP proteins polymerize via their ZPn subdomains, while ZPc subdomains modulate ZPn behavior. Using the model organism C. elegans, we investigated the aECM assembly of one ZP protein, LET-653, which shapes several tubes. Contrary to prevailing models, we find that LET-653 localizes and functions via its ZPc domain. Furthermore, we show that ZPc domain function requires cleavage at the LET-653 C-terminus, likely in part to relieve inhibition of the ZPc by the ZPn domain, but also to promote some other aspect of ZPc domain function. In vitro, the ZPc, but not ZPn, domain bound crystalline aggregates. These data offer a new model for ZP function whereby the ZPc domain is primarily responsible for matrix incorporation and tissue shaping.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1009188</identifier><identifier>PMID: 33141826</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Animals, Genetically Modified ; Biology and Life Sciences ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins - genetics ; Caenorhabditis elegans Proteins - metabolism ; Cell Line ; Drosophila ; Embryo, Nonmammalian ; Embryos ; Excretory system ; Extracellular matrix ; Extracellular Matrix - metabolism ; Incorporation ; Invertebrates ; Medicine and Health Sciences ; Membranes ; Models, Animal ; Mucins - genetics ; Mucins - metabolism ; Mutants ; Mutation ; Physical Sciences ; Physiological aspects ; Polymerization ; Protein Aggregates - genetics ; Protein Domains - genetics ; Proteins ; Research and Analysis Methods ; Zona pellucida</subject><ispartof>PLoS genetics, 2020-11, Vol.16 (11), p.e1009188-e1009188</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Cohen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cohen, Jennifer D</au><au>Bermudez, Jessica G</au><au>Good, Matthew C</au><au>Sundaram, Meera V</au><au>Nance, Jeremy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A C. elegans Zona Pellucida domain protein functions via its ZPc domain</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2020-11-03</date><risdate>2020</risdate><volume>16</volume><issue>11</issue><spage>e1009188</spage><epage>e1009188</epage><pages>e1009188-e1009188</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Zona Pellucida domain (ZP) proteins are critical components of the body's external-most protective layers, apical extracellular matrices (aECMs). Although their loss or dysfunction is associated with many diseases, it remains unclear how ZP proteins assemble in aECMs. Current models suggest that ZP proteins polymerize via their ZPn subdomains, while ZPc subdomains modulate ZPn behavior. Using the model organism C. elegans, we investigated the aECM assembly of one ZP protein, LET-653, which shapes several tubes. Contrary to prevailing models, we find that LET-653 localizes and functions via its ZPc domain. Furthermore, we show that ZPc domain function requires cleavage at the LET-653 C-terminus, likely in part to relieve inhibition of the ZPc by the ZPn domain, but also to promote some other aspect of ZPc domain function. In vitro, the ZPc, but not ZPn, domain bound crystalline aggregates. These data offer a new model for ZP function whereby the ZPc domain is primarily responsible for matrix incorporation and tissue shaping.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33141826</pmid><doi>10.1371/journal.pgen.1009188</doi><orcidid>https://orcid.org/0000-0002-6367-1034</orcidid><orcidid>https://orcid.org/0000-0002-2940-8750</orcidid><orcidid>https://orcid.org/0000-0001-8622-677X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Animals, Genetically Modified Biology and Life Sciences Caenorhabditis elegans Caenorhabditis elegans Proteins - genetics Caenorhabditis elegans Proteins - metabolism Cell Line Drosophila Embryo, Nonmammalian Embryos Excretory system Extracellular matrix Extracellular Matrix - metabolism Incorporation Invertebrates Medicine and Health Sciences Membranes Models, Animal Mucins - genetics Mucins - metabolism Mutants Mutation Physical Sciences Physiological aspects Polymerization Protein Aggregates - genetics Protein Domains - genetics Proteins Research and Analysis Methods Zona pellucida |
| title | A C. elegans Zona Pellucida domain protein functions via its ZPc domain |
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