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  LCP1 preferentially binds clasped alpha M beta 2 integrin and attenuates leukocyte adhesion under flow

Tseng, H.-Y., Samarelli, A. V., Kammerer, P., Scholze, S., Ziegler, T., Immler, R., et al. (2018). LCP1 preferentially binds clasped alpha M beta 2 integrin and attenuates leukocyte adhesion under flow. Journal of Cell Science, 131(22): UNSP jcs218214. doi:10.1242/jcs.218214.

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 Creators:
Tseng, Hui-Yuan1, Author              
Samarelli, Anna V.1, Author              
Kammerer, Patricia1, Author              
Scholze, Sarah1, Author              
Ziegler, Tilman1, Author              
Immler, Roland2, Author
Zent, Roy2, Author
Sperandio, Markus2, Author
Sanders, Charles R.2, Author
Fässler, Reinhard1, Author              
Böttcher, Ralph T.1, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2external, ou_persistent22              

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Free keywords: UBIQUITIN-LIKE DOMAIN; PROTEIN L-PLASTIN; BETA-INTEGRIN; FILAMIN BINDING; MOLECULAR-BASIS; ALPHA-ACTININ; TALIN HEAD; T-PLASTIN; ACTIVATION; CYTOSKELETONCell Biology; LCP1; Integrin inactivator; Leukocyte adhesion; Integrin interactome; Proteomics;
 Abstract: Integrins are alpha/beta heterodimers that interconvert between inactive and active states. In the active state the alpha/beta cytoplasmic domains recruit integrin-activating proteins and separate the transmembrane and cytoplasmic (TMcyto) domains (unclasped TMcyto). Conversely, in the inactive state the alpha/beta TMcyto domains bind integrin-inactivating proteins, resulting in the association of the TMcyto domains (clasped TMcyto). Here, we report the isolation of integrin cytoplasmic tail interactors using either lipid bicelle-incorporated integrin TMcyto domains (alpha 5, alpha M, alpha IIb, beta 1, beta 2 and beta 3 integrin TMcyto) or a clasped, lipid bicelle-incorporated alpha M beta 2 TMcyto. Among the proteins found to preferentially bind clasped rather than the isolated aM and beta 2 subunits was L-plastin (LCP1, also known as plastin-2), which binds to and maintains the inactive state of alpha M beta 2 integrin in vivo and thereby regulates leukocyte adhesion to integrin ligands under flow. Our findings offer a global view on cytoplasmic proteins interacting with different integrins and provide evidence for the existence of conformation-specific integrin interactors.

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Language(s): eng - English
 Dates: 2018-11
 Publication Status: Published online
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000451227400013
DOI: 10.1242/jcs.218214
 Degree: -

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Project name : -
Grant ID : 322652
Funding program : -
Funding organization : European Research Council

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Title: Journal of Cell Science
Source Genre: Journal
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Publ. Info: Cambridge, U.K. : Co. of Biologists
Pages: - Volume / Issue: 131 (22) Sequence Number: UNSP jcs218214 Start / End Page: - Identifier: ISSN: 0021-9533
CoNE: https://pure.mpg.de/cone/journals/resource/954925326678