A single E726Q mutation in the membrane proximal α-helix of integrin β3 subunit induces membrane blebbing by disrupting the membrane-actin cortex interaction.
- Author:
Yong-Kui KONG
1
;
Yue ZHANG
;
Ming-Hui LIN
;
Xiao-Dong XI
Author Information
1. Shanghai Institute of Hematology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
- Publication Type:Journal Article
- MeSH:
Animals;
CHO Cells;
Cell Surface Extensions;
Cricetinae;
Cricetulus;
Heterocyclic Compounds, 4 or More Rings;
chemistry;
Integrin beta3;
genetics;
Mutagenesis, Site-Directed;
Mutation;
Protein Structure, Tertiary
- From:
Journal of Experimental Hematology
2011;19(6):1450-1455
- CountryChina
- Language:Chinese
-
Abstract:
The membrane proximal α helix of integrin β subunit cytoplasmic tails plays an important functional role by interacting with various intracellular proteins, namely talin, α-actinin or skelemin. This study was designed to investigate the functional role of 5 highly conserved charged amino acids (R(724), K(725), E(726), E(731), E(733)) within this α helix by site-directed mutagenesis. The result showed that CHO cells expressing the αIIbβ3E726Q mutant had the most prominent phenotype and characterized by defective cell spreading on immobilized fibrinogen. In addition, this E726Q mutation induced membrane blebbing in cells adherent on fibrinogen, and this blebbing could be inhibited by the myosin light chain ATPase inhibitor blebbistatin. It is concluded that the membrane proximal α-helix of integrin β3 subunit is important in linking the phospholipid membrane to the submembraneous actin cortex.
