Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels

Nidhi Batra, Sirisha Burra, Arlene J. Siller-Jackson, Sumin Gu, Xuechun Xia, Gregory F. Weber, Douglas DeSimone, Lynda F. Bonewald, Eileen M. Lafer, Eugene Sprague, Martin A. Schwartz, Jean X. Jiang

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133 Scopus citations

Abstract

The connexin 43 (Cx43) hemichannel (HC) in the mechanosensory osteocytes is a major portal for the release of factors responsible for the anabolic effects of mechanical loading on bone formation and remodeling. However, little is known about how the Cx43 molecule responds to mechanical stimulation leading to the opening of the HC. Here, we demonstrate that integrin α5β1 interacts directly with Cx43 and that this interaction is required for mechanical stimulation-induced opening of the Cx43 HC. Direct mechanical perturbation via magnetic beads or conformational activation of integrin α5β1 leads to the opening of the Cx43 HC, and this role of the integrin is independent of its association with an extracellular fibronectin substrate. PI3K signaling is responsible for the shear stress-induced conformational activation of integrin α5β1 leading to the opening of the HC. These results identify an unconventional function of integrin that acts as a mechanical tether to induce opening of the HC and provide a mechanism connecting the effect of mechanical forces directly to anabolic function of the bone.

Original languageEnglish (US)
Pages (from-to)3359-3364
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number9
DOIs
StatePublished - Feb 28 2012

ASJC Scopus subject areas

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    Batra, N., Burra, S., Siller-Jackson, A. J., Gu, S., Xia, X., Weber, G. F., DeSimone, D., Bonewald, L. F., Lafer, E. M., Sprague, E., Schwartz, M. A., & Jiang, J. X. (2012). Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels. Proceedings of the National Academy of Sciences of the United States of America, 109(9), 3359-3364. https://doi.org/10.1073/pnas.1115967109