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) 10 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 Professor in the Biochemistry department at Medical College 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
