期刊
JOURNAL OF CELL SCIENCE
卷 126, 期 21, 页码 5030-5041出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.134528
关键词
Disulfide-restriction; Integrin clustering; Ligand-independent signaling
类别
资金
- National Basic Research Program of China [2010CB529703, 2014CB541905, 2012CB721002]
- National Natural Science Foundation of China [31190061, 31271487, 30970604, 31070641]
- Science and Technology Commission of Shanghai Municipality [11JC1414200]
- National 863 program of China [2012AA01A305]
- China Postdoctoral Science Foundation [2012T50445]
- Postdoctoral Research Program from SIBS [2012KIP503]
- SA-SIBS scholarship program
Control of integrin activation and signaling plays crucial roles in cell adhesion, spreading and migration. Here, we report that selective breakage of two conserved disulfide bonds located at the knees of integrin alpha(4)C589-C594 and beta(7)C494-C526 activated alpha(4)beta(7). This activated integrin had a unique structure that was different from the typical extended conformation of active integrin. In addition, these activated alpha(4)beta(7) integrins spontaneously clustered on the cell membrane and triggered integrin downstream signaling independent of ligand binding. Although these disulfide bonds were not broken during alpha(4)beta(7) activation by inside-out signaling or Mn2+, they could be specifically reduced by 0.1 mM dithiothreitol, a reducing strength that could be produced in vivo under certain conditions. Our findings reveal a novel mechanism of integrin activation under specific reducing conditions by which integrin can signal and promote cell spreading in the absence of ligand.
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