6 research outputs found
Improved Search for νμ→νe Oscillation in a Long-Baseline Accelerator Experiment
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Conversion of a Signal into Forces for Axon Outgrowth through Pak1-Mediated Shootin1 Phosphorylation
Get PDFSoluble guidance cues can direct cellular protrusion and migration by modulating adhesion and cytoskeletal dynamics. Actin filaments (F-actins) polymerize at the leading edge of motile cells and depolymerize proximally [1 and 2]; this, together with myosin II activity, induces retrograde flow of F-actins [3, 4 and 5]. It has been proposed that the traction forces underlying cellular motility may be regulated by the modulation of coupling efficiency between F-actin flow and the extracellular substrate via “clutch” molecules [6, 7, 8, 9 and 10]. However, how cell signaling controls the coupling efficiency remains unknown. Shootin1 functions as a linker molecule that couples F-actin retrograde flow and the substrate at neuronal growth cones to promote axon outgrowth [11]. Here we show that shootin1 is located at a critical interface, transducing a chemical signal into traction forces for axon outgrowth. We found that a chemoattractant, netrin-1, positively regulates traction forces at axonal growth cones via Pak1-mediated shootin1 phosphorylation. This phosphorylation enhanced the interaction between shootin1 and F-actin retrograde flow, thereby promoting F-actin-substrate coupling, force generation, and concomitant filopodium extension and axon outgrowth. These results suggest that dynamic actin-substrate coupling can transduce chemical signals into mechanical forces to control cellular motility and provide a molecular-level description of how this transduction may occur.journal articl
