LCP1 preferentially binds clasped ?M?2 integrin and attenuates leukocyte adhesion under flow.

ABSTRACT: Integrins are ?/? heterodimers that interconvert between inactive and active states. In the active state the ?/? cytoplasmic domains recruit integrin-activating proteins and separate the transmembrane and cytoplasmic (TMcyto) domains (unclasped TMcyto). Conversely, in the inactive state the ?/? 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 (?5, ?M, ?IIb, ?1, ?2 and ?3 integrin TMcyto) or a clasped, lipid bicelle-incorporated ?M?2 TMcyto. Among the proteins found to preferentially bind clasped rather than the isolated ?M and ?2 subunits was L-plastin (LCP1, also known as plastin-2), which binds to and maintains the inactive state of ?M?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.

SUBMITTER: Tseng HY 

PROVIDER: S-EPMC6262777 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature