The dual structural roles of the membrane distal region of the α-integrin cytoplasmic tail during integrin inside-out activation

Journal of Cell Science
Jiafu LiuJieqing Zhu

Abstract

Studies on the mechanism of integrin inside-out activation have been focused on the role of β-integrin cytoplasmic tails, which are relatively conserved and bear binding sites for the intracellular activators including talin and kindlin. Cytoplasmic tails for α-integrins share a conserved GFFKR motif at the membrane-proximal region and this forms a specific interface with the β-integrin membrane-proximal region to keep the integrin inactive. The α-integrin membrane-distal regions, after the GFFKR motif, are diverse both in length and sequence and their roles in integrin activation have not been well-defined. In this study, we report that the α-integrin cytoplasmic membrane-distal region contributes to maintaining integrin in the resting state and to integrin inside-out activation. Complete deletion of the α-integrin membrane-distal region diminished talin- and kindlin-mediated integrin ligand binding and conformational change. A proper length and suitable amino acids in α-integrin membrane-distal region was found to be important for integrin inside-out activation. Our data establish an essential role for the α-integrin cytoplasmic membrane-distal region in integrin activation and provide new insights into how talin and kindlin ...Continue Reading

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Citations

Sep 29, 2017·Molecular Biology of the Cell·Yunfeng ChenCheng Zhu
Oct 29, 2017·The Journal of Biological Chemistry·Zhengli WangJieqing Zhu
Jul 19, 2018·Blood·Dongwen ZhouJieqing Zhu
Sep 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Aye Myat Myat ThinnJieqing Zhu
Jul 17, 2020·Circulation Research·Chenghu ZhangDing Ai
Sep 27, 2018·Proceedings of the National Academy of Sciences of the United States of America·Krishna ChinthalapudiTina Izard
Aug 8, 2019·The Journal of Cell Biology·Ranjay JayadevDavid R Sherwood
Mar 20, 2020·Biophysical Journal·Zainab HaydariMohammad R K Mofrad

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