期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：47
页码：E7500-E7509
DOI：10.1073/pnas.1608767113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceCells directionally migrate in response to a variety of external cues, including chemical, electrical, and mechanical stimuli; however, only response to chemoattractants has been characterized at the molecular level. Binding of chemoattractants to specific surface receptors triggers rapid, transient activation of many signal transduction and cytoskeletal events. We discovered that brief application of shear stress to cells likely elicits activation of all of the same events. Responses to chemoattractants and shear stress are susceptible to many of the same perturbations, although that to mechanical stimulation uniquely is blocked by disruption of the actin cytoskeleton. Our finding provides insight into the molecular mechanism of cellular response to mechanical stimuli and has important implications for integration of chemical and mechanical inputs. Signal transduction pathways activated by chemoattractants have been extensively studied, but little is known about the events mediating responses to mechanical stimuli. We discovered that acute mechanical perturbation of cells triggered transient activation of all tested components of the chemotactic signal transduction network, as well as actin polymerization. Similarly to chemoattractants, the shear flow-induced signal transduction events displayed features of excitability, including the ability to mount a full response irrespective of the length of the stimulation and a refractory period that is shared with that generated by chemoattractants. Loss of G protein subunits, inhibition of multiple signal transduction events, or disruption of calcium signaling attenuated the response to acute mechanical stimulation. Unlike the response to chemoattractants, an intact actin cytoskeleton was essential for reacting to mechanical perturbation. These results taken together suggest that chemotactic and mechanical stimuli trigger activation of a common signal transduction network that integrates external cues to regulate cytoskeletal activity and drive cell migration.
