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Mechanical stress-activated integrin ?5?1 induces opening of connexin 43 hemichannels.

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 ?5?1 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 ?5?1 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 ?5?1 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.

SUBMITTER: Batra N 

PROVIDER: S-EPMC3295295 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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

Batra Nidhi N   Burra Sirisha S   Siller-Jackson Arlene J AJ   Gu Sumin S   Xia Xuechun X   Weber Gregory F GF   DeSimone Douglas D   Bonewald Lynda F LF   Lafer Eileen M EM   Sprague Eugene E   Schwartz Martin A MA   Jiang Jean X JX  

Proceedings of the National Academy of Sciences of the United States of America 20120213 9

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. D  ...[more]

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