The membrane-distal regions of integrin ? cytoplasmic domains contribute differently to integrin inside-out activation.

ABSTRACT: Functioning as signal receivers and transmitters, the integrin ?/? cytoplasmic tails (CT) are pivotal in integrin activation and signaling. 18 ? 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 ? CTMD region is essential for talin-induced integrin inside-out activation. However, it remains unknown whether the non-conserved ? CTMD regions differently regulate the inside-out activation of integrin. Using ?IIb?3, ?L?2, and ?5?1 as model integrins and by replacing their ? CTMD regions with those of ? subunits that pair with ?3, ?2, and ?1 subunits, we analyzed the function of CTMD regions of 17 ? subunits in talin-mediated integrin activation. We found that the ? 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 ? CTMD region. A membrane-proximal tyrosine residue present in the CTMD regions of a subset of ? integrins was identified to negatively regulate integrin inside-out activation. Our study provides a useful resource for investigating the function of ? integrin CTMD regions.

SUBMITTER: Thinn AMM 

PROVIDER: S-EPMC5864728 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature