Mechanical control of cyclic AMP signalling and gene transcription through integrins

Abstract

This study was carried out to discriminate between two alternative hypotheses as to how cells sense mechanical forces and transduce them into changes in gene transcription. Do cells sense mechanical signals through generalized membrane distortion1,2 or through specific transmembrane receptors, such as integrins3? Here we show that mechanical stresses applied to the cell surface alter the cyclic AMP signalling cascade and downstream gene transcription by modulating local release of signals generated by activated integrin receptors in a G-protein-dependent manner, whereas distortion of integrins in the absence of receptor occupancy has no effect.

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Figure 1: Stress-and integrin-dependent control of the cAMP signalling cascade.
Figure 2: Mechanistic analysis of integrin-dependent mechanotransduction.

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Acknowledgements

We thank M. Greenberg and S. Taylor for essential reagents, N. Wang and J. Fredberg for assistance with magnetic twisting cytometry, and J. Kornhauser, W. Wen, and G. Rodan for helpful suggestions. This work was supported by grants from NIH (CA55833 and HL33009) and NASA (NAG5-4839), NIH Dentist Scientist award to Harvard School of Dental Medicine (DE00275 to C.M.), and a Howard Hughes predoctoral fellowship (F.A.).

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Correspondence to Donald E. Ingber.

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