Integrity of Narrow Epithelial Tubes in the C. elegans Excretory System Requires a Transient Luminal Matrix
Identifieur interne : 000874 ( Pmc/Checkpoint ); précédent : 000873; suivant : 000875Integrity of Narrow Epithelial Tubes in the C. elegans Excretory System Requires a Transient Luminal Matrix
Auteurs : Hasreet K. Gill [États-Unis] ; Jennifer D. Cohen [États-Unis] ; Jesus Ayala-Figueroa [États-Unis] ; Rachel Forman-Rubinsky [États-Unis] ; Corey Poggioli [États-Unis] ; Kevin Bickard [États-Unis] ; Jean M. Parry [États-Unis] ; Pu Pu [États-Unis] ; David H. Hall [États-Unis] ; Meera V. Sundaram [États-Unis]Source :
- PLoS Genetics [ 1553-7390 ] ; 2016.
Abstract
Most epithelial cells secrete a glycoprotein-rich apical extracellular matrix that can have diverse but still poorly understood roles in development and physiology. Zona Pellucida (ZP) domain glycoproteins are common constituents of these matrices, and their loss in humans is associated with a number of diseases. Understanding of the functions, organization and regulation of apical matrices has been hampered by difficulties in imaging them both
Url:
DOI: 10.1371/journal.pgen.1006205
PubMed: 27482894
PubMed Central: 4970718
Affiliations:
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. <italic>elegans</italic>
Excretory System Requires a Transient Luminal Matrix</title>
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Excretory System Requires a Transient Luminal Matrix</title>
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<front><div type="abstract" xml:lang="en"><p>Most epithelial cells secrete a glycoprotein-rich apical extracellular matrix that can have diverse but still poorly understood roles in development and physiology. Zona Pellucida (ZP) domain glycoproteins are common constituents of these matrices, and their loss in humans is associated with a number of diseases. Understanding of the functions, organization and regulation of apical matrices has been hampered by difficulties in imaging them both <italic>in vivo</italic>
and <italic>ex vivo</italic>
. We identified the PAN-Apple, mucin and ZP domain glycoprotein LET-653 as an early and transient apical matrix component that shapes developing epithelia in <italic>C</italic>
. <italic>elegans</italic>
. LET-653 has modest effects on shaping of the vulva and epidermis, but is essential to prevent lumen fragmentation in the very narrow, unicellular excretory duct tube. We were able to image the transient LET-653 matrix by both live confocal imaging and transmission electron microscopy. Structure/function and fluorescence recovery after photobleaching studies revealed that LET-653 exists in two separate luminal matrix pools, a loose fibrillar matrix in the central core of the lumen, to which it binds dynamically via its PAN domains, and an apical-membrane-associated matrix, to which it binds stably via its ZP domain. The PAN domains are both necessary and sufficient to confer a cyclic pattern of duct lumen localization that precedes each molt, while the ZP domain is required for lumen integrity. Ectopic expression of full-length LET-653, but not the PAN domains alone, could expand lumen diameter in the developing gut tube, where LET-653 is not normally expressed. Together, these data support a model in which the PAN domains regulate the ability of the LET-653 ZP domain to interact with other factors at the apical membrane, and this ZP domain interaction promotes expansion and maintenance of lumen diameter. These data identify a transient apical matrix component present prior to cuticle secretion in <italic>C</italic>
. <italic>elegans</italic>
, demonstrate critical roles for this matrix component in supporting lumen integrity within narrow bore tubes such as those found in the mammalian microvasculature, and reveal functional importance of the evolutionarily conserved ZP domain in this tube protecting activity.</p>
</div>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Genet</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS Genet</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosgen</journal-id>
<journal-title-group><journal-title>PLoS Genetics</journal-title>
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<issn pub-type="ppub">1553-7390</issn>
<issn pub-type="epub">1553-7404</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, CA USA</publisher-loc>
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<article-meta><article-id pub-id-type="pmid">27482894</article-id>
<article-id pub-id-type="pmc">4970718</article-id>
<article-id pub-id-type="doi">10.1371/journal.pgen.1006205</article-id>
<article-id pub-id-type="publisher-id">PGENETICS-D-15-00500</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Developmental Biology</subject>
<subj-group><subject>Embryology</subject>
<subj-group><subject>Embryos</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Anatomy</subject>
<subj-group><subject>Reproductive System</subject>
<subj-group><subject>Genital Anatomy</subject>
<subj-group><subject>Vulva</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Anatomy</subject>
<subj-group><subject>Reproductive System</subject>
<subj-group><subject>Genital Anatomy</subject>
<subj-group><subject>Vulva</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Biochemistry</subject>
<subj-group><subject>Proteins</subject>
<subj-group><subject>Protein Domains</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject>
<subj-group><subject>Microscopy</subject>
<subj-group><subject>Light Microscopy</subject>
<subj-group><subject>Fluorescence Recovery after Photobleaching</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Developmental Biology</subject>
<subj-group><subject>Metamorphosis</subject>
<subj-group><subject>Larvae</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Cell Biology</subject>
<subj-group><subject>Cellular Structures and Organelles</subject>
<subj-group><subject>Cell Membranes</subject>
<subj-group><subject>Membrane Fusion</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Physiology</subject>
<subj-group><subject>Physiological Processes</subject>
<subj-group><subject>Secretion</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Physiology</subject>
<subj-group><subject>Physiological Processes</subject>
<subj-group><subject>Secretion</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject>
<subj-group><subject>Model Organisms</subject>
<subj-group><subject>Animal Models</subject>
<subj-group><subject>Caenorhabditis Elegans</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Animals</subject>
<subj-group><subject>Invertebrates</subject>
<subj-group><subject>Nematoda</subject>
<subj-group><subject>Caenorhabditis</subject>
<subj-group><subject>Caenorhabditis Elegans</subject>
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<title-group><article-title>Integrity of Narrow Epithelial Tubes in the <italic>C</italic>
. <italic>elegans</italic>
Excretory System Requires a Transient Luminal Matrix</article-title>
<alt-title alt-title-type="running-head"><italic>C</italic>
. <italic>elegans</italic>
Luminal Zona Pellucida Domain Protein</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Gill</surname>
<given-names>Hasreet K.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Cohen</surname>
<given-names>Jennifer D.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ayala-Figueroa</surname>
<given-names>Jesus</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-1853-9456</contrib-id>
<name><surname>Forman-Rubinsky</surname>
<given-names>Rachel</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-9589-6297</contrib-id>
<name><surname>Poggioli</surname>
<given-names>Corey</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-4523-7648</contrib-id>
<name><surname>Bickard</surname>
<given-names>Kevin</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Parry</surname>
<given-names>Jean M.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pu</surname>
<given-names>Pu</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hall</surname>
<given-names>David H.</given-names>
</name>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-2940-8750</contrib-id>
<name><surname>Sundaram</surname>
<given-names>Meera V.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
</contrib-group>
<aff id="aff001"><label>1</label>
<addr-line>Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America</addr-line>
</aff>
<aff id="aff002"><label>2</label>
<addr-line>Department of Biology, Georgian Court University, Lakewood, New Jersey, United States of America</addr-line>
</aff>
<aff id="aff003"><label>3</label>
<addr-line>Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Chisholm</surname>
<given-names>Andrew D.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>University of California San Diego, UNITED STATES</addr-line>
</aff>
<author-notes><fn fn-type="conflict" id="coi001"><p>The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: MVS HKG JDC. Performed the experiments: HKG JDC JAF RFR CP KB JMP PP MVS. Analyzed the data: MVS HKG JDC. Contributed reagents/materials/analysis tools: JMP DHH. Wrote the paper: MVS HKG JDC.</p>
</fn>
<corresp id="cor001">* E-mail: <email>sundaram@mail.med.upenn.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="epub"><day>2</day>
<month>8</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection"><month>8</month>
<year>2016</year>
</pub-date>
<volume>12</volume>
<issue>8</issue>
<elocation-id>e1006205</elocation-id>
<history><date date-type="received"><day>27</day>
<month>2</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>28</day>
<month>6</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>© 2016 Gill et al</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>Gill et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="pgen.1006205.pdf"></self-uri>
<abstract><p>Most epithelial cells secrete a glycoprotein-rich apical extracellular matrix that can have diverse but still poorly understood roles in development and physiology. Zona Pellucida (ZP) domain glycoproteins are common constituents of these matrices, and their loss in humans is associated with a number of diseases. Understanding of the functions, organization and regulation of apical matrices has been hampered by difficulties in imaging them both <italic>in vivo</italic>
and <italic>ex vivo</italic>
. We identified the PAN-Apple, mucin and ZP domain glycoprotein LET-653 as an early and transient apical matrix component that shapes developing epithelia in <italic>C</italic>
. <italic>elegans</italic>
. LET-653 has modest effects on shaping of the vulva and epidermis, but is essential to prevent lumen fragmentation in the very narrow, unicellular excretory duct tube. We were able to image the transient LET-653 matrix by both live confocal imaging and transmission electron microscopy. Structure/function and fluorescence recovery after photobleaching studies revealed that LET-653 exists in two separate luminal matrix pools, a loose fibrillar matrix in the central core of the lumen, to which it binds dynamically via its PAN domains, and an apical-membrane-associated matrix, to which it binds stably via its ZP domain. The PAN domains are both necessary and sufficient to confer a cyclic pattern of duct lumen localization that precedes each molt, while the ZP domain is required for lumen integrity. Ectopic expression of full-length LET-653, but not the PAN domains alone, could expand lumen diameter in the developing gut tube, where LET-653 is not normally expressed. Together, these data support a model in which the PAN domains regulate the ability of the LET-653 ZP domain to interact with other factors at the apical membrane, and this ZP domain interaction promotes expansion and maintenance of lumen diameter. These data identify a transient apical matrix component present prior to cuticle secretion in <italic>C</italic>
. <italic>elegans</italic>
, demonstrate critical roles for this matrix component in supporting lumen integrity within narrow bore tubes such as those found in the mammalian microvasculature, and reveal functional importance of the evolutionarily conserved ZP domain in this tube protecting activity.</p>
</abstract>
<abstract abstract-type="summary"><title>Author Summary</title>
<p>Most organs in the body are made up of networks of tubes that transport fluids or gases. These tubes come in many different sizes and shapes, with some narrow capillaries being only one cell in diameter. As tubes develop and take their final shapes, they secrete various glycoproteins into their hollow interior or lumen. The functions of these luminal proteins are not well understood, but there is increasing evidence that they are important for lumen shaping and that their loss can contribute to diseases such as cardiovascular disease and chronic kidney disease. Through studies of the nematode <italic>C</italic>
. <italic>elegans</italic>
, we identified a luminal glycoprotein, LET-653, that is transiently expressed in multiple developing tube types but is particularly critical to maintain integrity of the narrowest, unicellular tubes. We identified protein domains that direct LET-653 to specific apical matrix compartments and mediate its oscillatory pattern of lumen localization. Furthermore, we showed that the LET-653 tube-protecting activity depends on a Zona Pellucida (ZP) domain similar to that found in the mammalian egg-coat and in many other luminal or sensory matrix proteins involved in human disease.</p>
</abstract>
<funding-group><award-group id="award001"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>GM58540</award-id>
<principal-award-recipient>Meera Sundaram</principal-award-recipient>
</award-group>
<award-group id="award002"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>OD010943</award-id>
<principal-award-recipient><name><surname>Hall</surname>
<given-names>David H</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award003"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000001</institution-id>
<institution>National Science Foundation</institution>
</institution-wrap>
</funding-source>
<award-id>1257879</award-id>
<principal-award-recipient>Meera Sundaram</principal-award-recipient>
</award-group>
<funding-statement>This work was funded by National Institutes of Health grant R01GM58540 and National Science Foundation grant 1257879 to MVS. DHH, his EM archive, and the website <ext-link ext-link-type="uri" xlink:href="http://www.Wormimage.org">www.Wormimage.org</ext-link>
are supported by NIH OD010943. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts><fig-count count="13"></fig-count>
<table-count count="0"></table-count>
<page-count count="32"></page-count>
</counts>
<custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name>
<meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes><title>Data Availability</title>
<p>All relevant data are within the paper and its Supporting Information files.</p>
</notes>
</front>
</pmc>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>New Jersey</li>
<li>Pennsylvanie</li>
<li>État de New York</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Gill, Hasreet K" sort="Gill, Hasreet K" uniqKey="Gill H" first="Hasreet K." last="Gill">Hasreet K. Gill</name>
</region>
<name sortKey="Ayala Figueroa, Jesus" sort="Ayala Figueroa, Jesus" uniqKey="Ayala Figueroa J" first="Jesus" last="Ayala-Figueroa">Jesus Ayala-Figueroa</name>
<name sortKey="Bickard, Kevin" sort="Bickard, Kevin" uniqKey="Bickard K" first="Kevin" last="Bickard">Kevin Bickard</name>
<name sortKey="Cohen, Jennifer D" sort="Cohen, Jennifer D" uniqKey="Cohen J" first="Jennifer D." last="Cohen">Jennifer D. Cohen</name>
<name sortKey="Forman Rubinsky, Rachel" sort="Forman Rubinsky, Rachel" uniqKey="Forman Rubinsky R" first="Rachel" last="Forman-Rubinsky">Rachel Forman-Rubinsky</name>
<name sortKey="Hall, David H" sort="Hall, David H" uniqKey="Hall D" first="David H." last="Hall">David H. Hall</name>
<name sortKey="Parry, Jean M" sort="Parry, Jean M" uniqKey="Parry J" first="Jean M." last="Parry">Jean M. Parry</name>
<name sortKey="Parry, Jean M" sort="Parry, Jean M" uniqKey="Parry J" first="Jean M." last="Parry">Jean M. Parry</name>
<name sortKey="Poggioli, Corey" sort="Poggioli, Corey" uniqKey="Poggioli C" first="Corey" last="Poggioli">Corey Poggioli</name>
<name sortKey="Pu, Pu" sort="Pu, Pu" uniqKey="Pu P" first="Pu" last="Pu">Pu Pu</name>
<name sortKey="Sundaram, Meera V" sort="Sundaram, Meera V" uniqKey="Sundaram M" first="Meera V." last="Sundaram">Meera V. Sundaram</name>
</country>
</tree>
</affiliations>
</record>
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