title: The importance of claudin-7 palmitoylation on membrane subdomain localization and metastasis-promoting activities creator: Heiler, Sarah creator: Mu, Wei creator: Zöller, Margot creator: Thuma, Florian subject: ddc-610 subject: 610 Medical sciences Medicine description: Background: Claudin-7 (cld7), a tight junction (TJ) component, is also found basolaterally and in the cytoplasm. Basolaterally located cld7 is enriched in glycolipid-enriched membrane domains (GEM), where it associates with EpCAM (EpC). The conditions driving cld7 out of TJ into GEM, which is associated with a striking change in function, were not defined. Thus, we asked whether cld7 serines or palmitoylation affect cld7 location and protein, particularly EpCAM, associations. Results: HEK cells were transfected with EpCAM and wild type cld7 or cld7, where serine phopsphorylation or the palmitoylation sites (AA184, AA186) (cld7mPalm) were mutated. Exchange of individual serine phosphorylation sites did not significantly affect the GEM localization and the EpCAM association. Instead, cld7mPalm was poorly recruited into GEM. This has consequences on migration and invasiveness as palmitoylated cld7 facilitates integrin and EpCAM recruitment, associates with cytoskeletal linker proteins and cooperates with MMP14, CD147 and TACE, which support motility, matrix degradation and EpCAM cleavage. On the other hand, only cld7mPalm associates with TJ proteins. Conclusion: Cld7 palmitoylation prohibits TJ integration and fosters GEM recruitment. Via associated molecules, palmitoylated cld7 supports motility and invasion. publisher: Biomed Central date: 2015 type: Article type: info:eu-repo/semantics/article type: NonPeerReviewed format: application/pdf identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/19350/1/12964_2015_Article_105.pdf identifier: DOI: identifier: urn:nbn:de:bsz:16-heidok-193506 identifier: Heiler, Sarah ; Mu, Wei ; Zöller, Margot ; Thuma, Florian (2015) The importance of claudin-7 palmitoylation on membrane subdomain localization and metastasis-promoting activities. Cell communication and signaling, 13 (29). pp. 1-17. ISSN 1478-811X relation: https://archiv.ub.uni-heidelberg.de/volltextserver/19350/ rights: info:eu-repo/semantics/openAccess rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id) language: eng