The membrane-distal regions of integrin α cytoplasmic domains contribute differently to integrin inside-out activation. Sci Rep 2018 Mar 22;8(1):5067
Date
03/24/2018Pubmed ID
29568062Pubmed Central ID
PMC5864728DOI
10.1038/s41598-018-23444-wScopus ID
2-s2.0-85044319699 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
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.
Author List
Thinn AMM, Wang Z, Zhu JAuthor
Jieqing Zhu PhD Assistant Professor, Associate Investigator in the Biochemistry department at BloodCenter of WisconsinMESH terms used to index this publication - Major topics in bold
Amino AcidsAnimals
Cell Membrane
Cytoplasm
Cytoplasmic Structures
HEK293 Cells
Humans
Integrin alpha Chains
Integrin beta Chains
Mice
Protein Conformation
Protein Domains
Talin
Tyrosine
