response to mechanical stress is mediated by the trpa channel painless in the drosophila heart响应机械应力是由trpa通道无痛的果蝇心脏.pdfVIP

Response to Mechanical Stress Is Mediated by the TRPA Channel Painless in the Drosophila Heart ´ ´ ´ ´ ´ Sebastien Senatore, Vatrapu Rami Reddy, Michel Semeriva, Laurent Perrin, Nathalie Lalevee* ´ ´ ´ ´ Institut de Biologie du developpement de Marseille-Luminy, UMR-CNRS 6216, Universite de la Mediterranee, Marseille, France Abstract Mechanotransduction modulates cellular functions as diverse as migration, proliferation, differentiation, and apoptosis. It is crucial for organ development and homeostasis and leads to pathologies when defective. However, despite considerable efforts made in the past, the molecular basis of mechanotransduction remains poorly understood. Here, we have investigated the genetic basis of mechanotransduction in Drosophila. We show that the fly heart senses and responds to mechanical forces by regulating cardiac activity. In particular, pauses in heart activity are observed under acute mechanical constraints in vivo. We further confirm by a variety of in situ tests that these cardiac arrests constitute the biological force- induced response. In order to identify molecular components of the mechanotransduction pathway, we carried out a genetic screen based on the dependence of cardiac activity upon mechanical constraints and identified Painless, a TRPA channel. We observe a clear absence of in vivo cardiac arrest following inactivation of painless and further demonstrate that painless is autonomously required in the heart to mediate the response to mechanical stress. Furthermore, direct activation of Painless is sufficient to produce pauses in hear