Cell Biology

A Forced Opening

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Science  02 Mar 2012:
Vol. 335, Issue 6072, pp. 1021-1022
DOI: 10.1126/science.335.6072.1021-c

Mechanical forces on bone stimulate intracellular signaling pathways in osteocytes that promote remodeling. Signaling molecules that drive such remodeling are likely transmitted between cells through the connexin 43 (Cx43) hemichannel (HC). Integrins are focal adhesion proteins that provide support to the cell by connecting the cytoskeleton to extracellular matrix (ECM) components like fibronectin. Integrins have also been proposed to be mechanosensors in bone cells. Batra et al. now show that the cytoplasmic domain of the α subunit of integrin α5β1 interacts with the cytoplasmic domain of Cx43, that the interaction is strengthened by fluid flow, and that this interaction is required for HC opening. The opening required osteocyte attachment to the ECM but was independent of integrin α5β1 binding to its ligand, fibronectin. Direct forces applied to integrin α5β1 by magnetic beads induced the opening of the HC, and such mechanical stress–induced opening required phosphatidylinositol 3-kinase (PI3K), which has been implicated in fluid-flow–induced activation of integrins in epithelial cells. It is likely that PI3K is responsive to fluid flow and transmits this to integrins, leading to opening of the HC and bone remodeling.

Proc. Natl. Acad. Sci. U.S.A. 109, 10.1073/pnas.1115967109 (2012).

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