Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-α4β1 integrin interaction, cell adhesion and anti-proliferative activity
Identifieur interne : 000347 ( Main/Exploration ); précédent : 000346; suivant : 000348Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-α4β1 integrin interaction, cell adhesion and anti-proliferative activity
Auteurs : Orlando Maiorani [Italie] ; Eliana Pivetta [Italie] ; Alessandra Capuano [Italie] ; Teresa Maria Elisa Modica [Italie] ; Bruna Wassermann [Italie] ; Francesco Bucciotti [Italie] ; Alfonso Colombatti [Italie] ; Roberto Doliana [Italie] ; Paola Spessotto [Italie]Source :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
The extracellular matrix glycoprotein EMILIN1 exerts a wide range of functions mainly associated with its gC1q domain. Besides providing functional significance for adhesion and migration, the direct interaction between α4β1 integrin and EMILIN1-gC1q regulates cell proliferation, transducing net anti-proliferative effects. We have previously demonstrated that EMILIN1 degradation by neutrophil elastase (NE) is a specific mechanism leading to the loss of functions disabling its regulatory properties. In this study we further analysed the proteolytic activity of NE, MMP-3, MMP-9, and MT1-MMP on EMILIN1 and found that MMP-3 and MT1-MMP partially cleaved EMILIN1 but without affecting the functional properties associated with the gC1q domain, whereas NE was able to fully impair the interaction of gC1q with the α4β1 integrin by cleaving this domain outside of the E933 integrin binding site. By a site direct mutagenesis approach we mapped the bond between S913 and R914 residues and selected the NE-resistant R914W mutant still able to interact with the α4β1 integrin after NE treatment. Functional studies showed that NE impaired the EMILIN1-α4β1 integrin interaction by cleaving the gC1q domain in a region crucial for its proper structural conformation, paving the way to better understand NE effects on EMILIN1-cell interaction in pathological context.
Url:
DOI: 10.1038/srep39974
PubMed: 28074935
PubMed Central: 5225433
Affiliations:
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activity</title><author><name sortKey="Maiorani, Orlando" sort="Maiorani, Orlando" uniqKey="Maiorani O" first="Orlando" last="Maiorani">Orlando Maiorani</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute</institution>, Aviano 33081,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pivetta, Eliana" sort="Pivetta, Eliana" uniqKey="Pivetta E" first="Eliana" last="Pivetta">Eliana Pivetta</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute</institution>, Aviano 33081,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Capuano, Alessandra" sort="Capuano, Alessandra" uniqKey="Capuano A" first="Alessandra" last="Capuano">Alessandra Capuano</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute</institution>, Aviano 33081,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Modica, Teresa Maria Elisa" sort="Modica, Teresa Maria Elisa" uniqKey="Modica T" first="Teresa Maria Elisa" last="Modica">Teresa Maria Elisa Modica</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute</institution>, Aviano 33081,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wassermann, Bruna" sort="Wassermann, Bruna" uniqKey="Wassermann B" first="Bruna" last="Wassermann">Bruna Wassermann</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute</institution>, Aviano 33081,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bucciotti, Francesco" sort="Bucciotti, Francesco" uniqKey="Bucciotti F" first="Francesco" last="Bucciotti">Francesco Bucciotti</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute</institution>, Aviano 33081,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Colombatti, Alfonso" sort="Colombatti, Alfonso" uniqKey="Colombatti A" first="Alfonso" last="Colombatti">Alfonso Colombatti</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute</institution>, Aviano 33081,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Doliana, Roberto" sort="Doliana, Roberto" uniqKey="Doliana R" first="Roberto" last="Doliana">Roberto Doliana</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute</institution>, Aviano 33081,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Spessotto, Paola" sort="Spessotto, Paola" uniqKey="Spessotto P" first="Paola" last="Spessotto">Paola Spessotto</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Experimental Oncology 2, Department of Translational Research, CRO-IRCCS, National Cancer Institute</institution>, Aviano 33081,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The extracellular matrix glycoprotein EMILIN1 exerts a wide range of functions mainly associated with its gC1q domain. Besides providing functional significance for adhesion and migration, the direct interaction between α4β1 integrin and EMILIN1-gC1q regulates cell proliferation, transducing net anti-proliferative effects. We have previously demonstrated that EMILIN1 degradation by neutrophil elastase (NE) is a specific mechanism leading to the loss of functions disabling its regulatory properties. In this study we further analysed the proteolytic activity of NE, MMP-3, MMP-9, and MT1-MMP on EMILIN1 and found that MMP-3 and MT1-MMP partially cleaved EMILIN1 but without affecting the functional properties associated with the gC1q domain, whereas NE was able to fully impair the interaction of gC1q with the α4β1 integrin by cleaving this domain outside of the E933 integrin binding site. By a site direct mutagenesis approach we mapped the bond between S913 and R914 residues and selected the NE-resistant R914W mutant still able to interact with the α4β1 integrin after NE treatment. Functional studies showed that NE impaired the EMILIN1-α4β1 integrin interaction by cleaving the gC1q domain in a region crucial for its proper structural conformation, paving the way to better understand NE effects on EMILIN1-cell interaction in pathological context.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hynes, R O" uniqKey="Hynes R">R. O. Hynes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Watt, F M" uniqKey="Watt F">F. M. Watt</name></author><author><name sortKey="Fujiwara, H" uniqKey="Fujiwara H">H. Fujiwara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Streuli, C H" uniqKey="Streuli C">C. H. Streuli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moreno Layseca, P" uniqKey="Moreno Layseca P">P. Moreno-Layseca</name></author><author><name sortKey="Streuli, C H" uniqKey="Streuli C">C. H. 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Xing</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Italie</li></country></list><tree><country name="Italie"><noRegion><name sortKey="Maiorani, Orlando" sort="Maiorani, Orlando" uniqKey="Maiorani O" first="Orlando" last="Maiorani">Orlando Maiorani</name></noRegion><name sortKey="Bucciotti, Francesco" sort="Bucciotti, Francesco" uniqKey="Bucciotti F" first="Francesco" last="Bucciotti">Francesco Bucciotti</name><name sortKey="Capuano, Alessandra" sort="Capuano, Alessandra" uniqKey="Capuano A" first="Alessandra" last="Capuano">Alessandra Capuano</name><name sortKey="Colombatti, Alfonso" sort="Colombatti, Alfonso" uniqKey="Colombatti A" first="Alfonso" last="Colombatti">Alfonso Colombatti</name><name sortKey="Doliana, Roberto" sort="Doliana, Roberto" uniqKey="Doliana R" first="Roberto" last="Doliana">Roberto Doliana</name><name sortKey="Modica, Teresa Maria Elisa" sort="Modica, Teresa Maria Elisa" uniqKey="Modica T" first="Teresa Maria Elisa" last="Modica">Teresa Maria Elisa Modica</name><name sortKey="Pivetta, Eliana" sort="Pivetta, Eliana" uniqKey="Pivetta E" first="Eliana" last="Pivetta">Eliana Pivetta</name><name sortKey="Spessotto, Paola" sort="Spessotto, Paola" uniqKey="Spessotto P" first="Paola" last="Spessotto">Paola Spessotto</name><name sortKey="Wassermann, Bruna" sort="Wassermann, Bruna" uniqKey="Wassermann B" first="Bruna" last="Wassermann">Bruna Wassermann</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|area= LymphedemaV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:5225433
|texte= Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-α4β1 integrin interaction, cell adhesion and anti-proliferative activity
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:28074935" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a LymphedemaV1
| This area was generated with Dilib version V0.6.31. |  |