eprintid: 19350
rev_number: 27
eprint_status: archive
userid: 1589
dir: disk0/00/01/93/50
datestamp: 2015-11-25 10:12:29
lastmod: 2024-04-28 21:20:07
status_changed: 2015-11-25 10:12:29
type: article
metadata_visibility: show
creators_name: Heiler, Sarah
creators_name: Mu, Wei
creators_name: Zöller, Margot
creators_name: Thuma, Florian
title: The importance of claudin-7 palmitoylation on membrane subdomain localization and metastasis-promoting activities
subjects: ddc-610
divisions: i-850300
divisions: i-910200
abstract: 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.  
date: 2015
publisher: Biomed Central
id_scheme: DOI
ppn_swb: 165355441X
own_urn: urn:nbn:de:bsz:16-heidok-193506
language: eng
bibsort: HEILERSARATHEIMPORTA2015
full_text_status: public
publication: Cell communication and signaling
volume: 13
number: 29
place_of_pub: London
pagerange: 1-17
issn: 1478-811X
citation:   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     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/19350/1/12964_2015_Article_105.pdf