Show simple item record

dc.contributor.authorKlapholz, Benjaminen
dc.contributor.authorHerbert, Samantha Len
dc.contributor.authorWellmann, Juttaen
dc.contributor.authorJohnson, Roberten
dc.contributor.authorParsons, Maddyen
dc.contributor.authorBrown, Nicholasen
dc.date.accessioned2015-04-01T10:57:27Z
dc.date.available2015-04-01T10:57:27Z
dc.date.issued2015-03-05en
dc.identifier.citationCurrent Biology Volume 25, Issue 7, p847–857, 30 March 2015. DOI: 10.1016/j.cub.2015.01.043en
dc.identifier.issn0960-9822
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/247244
dc.description.abstractCell-matrix adhesion is essential for building animals, promoting tissue cohesion, and enabling cells to migrate and resist mechanical force. Talin is an intracellular protein that is critical for linking integrin extracellular-matrix receptors to the actin cytoskeleton. A key question raised by structure-function studies is whether talin, which is critical for all integrin-mediated adhesion, acts in the same way in every context. We show that distinct combinations of talin domains are required for each of three different integrin functions during Drosophila development. The partial function of some mutant talins requires vinculin, indicating that recruitment of vinculin allows talin to duplicate its own activities. The different requirements are best explained by alternative mechanisms of talin function, with talin using one or both of its integrin-binding sites. We confirmed these alternatives by showing that the proximity between the second integrin-binding site and integrins differs, suggesting that talin adopts different orientations relative to integrins. Finally, we show that vinculin and actomyosin activity help change talin’s orientation. These findings demonstrate that the mechanism of talin function differs in each developmental context examined. The different arrangements of the talin molecule relative to integrins suggest that talin is able to sense different force vectors, either parallel or perpendicular to the membrane. This provides a paradigm for proteins whose apparent uniform function is in fact achieved by a variety of distinct mechanisms involving different molecular architectures.
dc.description.sponsorshipThis work was supported by grants from the Wellcome Trust (069943 and 086451) and the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/L006669/1) to N.H.B., a BBSRC studentship to J.W. (BB/D526102/1), and a grant from the Royal Society and Medical Research Council (MR/K015664/1) to M.P.
dc.languageEnglishen
dc.language.isoenen
dc.publisherCell/Elsevier
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.titleAlternative Mechanisms for Talin to Mediate Integrin Functionen
dc.typeArticle
dc.description.versionThis is the final published version. It first appeared at http://www.cell.com/current-biology/fulltext/S0960-9822%2815%2900075-5.en
prism.endingPage857
prism.publicationDate2015en
prism.publicationNameCurrent Biologyen
prism.startingPage847
prism.volume25en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderBBSRC
dc.rioxxterms.funderMRC
dc.rioxxterms.projectid069943
dc.rioxxterms.projectid086451
dc.rioxxterms.projectidBB/L006669/1
dc.rioxxterms.projectidBB/D526102/1
dc.rioxxterms.projectidMR/K015664/1
dcterms.dateAccepted2015-01-19en
rioxxterms.versionofrecord10.1016/j.cub.2015.01.043en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-03-05en
dc.contributor.orcidKlapholz, Benjamin [0000-0002-3681-4415]
dc.contributor.orcidBrown, Nicholas [0000-0002-8958-7017]
dc.identifier.eissn1879-0445
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/L006669/1)
pubs.funder-project-idWellcome Trust (086451/Z/08/Z)
pubs.funder-project-idBBSRC (BB/D526102/1)
pubs.funder-project-idWellcome Trust (069943/Z/02/Z)


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales