The membrane-distal regions of integrin α cytoplasmic domains contribute differently to integrin inside-out activation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Aye Myat Myat Thinn, Zhengli Wang, Jieqing Zhu

ABSTRACT

Functioning as signal receivers and transmitters, the integrin α/β cytoplasmic tails (CT) are pivotal in integrin activation and signaling. 18 α integrin subunits share a conserved membrane-proximal region but have a highly diverse membrane-distal (MD) region at their CTs. Recent studies demonstrated that the presence of α CTMD region is essential for talin-induced integrin inside-out activation. However, it remains unknown whether the non-conserved α CTMD regions differently regulate the inside-out activation of integrin. Using αIIbβ3, αLβ2, and α5β1 as model integrins and by replacing their α CTMD regions with those of α subunits that pair with β3, β2, and β1 subunits, we analyzed the function of CTMD regions of 17 α subunits in talin-mediated integrin activation. We found that the α CTMD regions play two roles on integrin, which are activation-supportive and activation-regulatory. The regulatory but not the supportive function depends on the sequence identity of α CTMD region. A membrane-proximal tyrosine residue present in the CTMD regions of a subset of α integrins was identified to negatively regulate integrin inside-out activation. Our study provides a useful resource for investigating the function of α integrin CTMD regions. More... »

PAGES

5067

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-23444-w

    DOI

    http://dx.doi.org/10.1038/s41598-018-23444-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1101671989

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29568062


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