TY - JOUR T1 - Diverse roles of guanine nucleotide exchange factors in regulating collective cell migration JF - bioRxiv DO - 10.1101/076125 SP - 076125 AU - Assaf Zaritsky AU - Yun-Yu Tseng AU - M. Angeles Rabadán AU - Michael Overholtzer AU - Gaudenz Danuser AU - Alan Hall Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/09/21/076125.abstract N2 - Efficient collective migration depends on a balance between contractility and cytoskeletal rearrangements, adhesion, and mechanical cell-cell communication, which are all controlled by GTPases of the RHO family. Here, we report the results of a comprehensive screen assessing the contributions of the guanine nucleotide exchange factors (GEFs) to the regulation of this process during the wound healing response of a scratched human bronchial epithelial cell monolayer. Our studies uncovered GEFs that are required for collective motility at large, such as SOS1 and β-PIX, and RHOA GEFs ARHGEF18, ARHGEF11, ARHGEF3 and ARHGEF28 that are implicated in intercellular communication. Downregulation of these GEFs differentially enhance front-to-back propagation of guidance cues through the cell monolayer. These effects are partially mirrored by downregulation of RHOA expression and myosin-II activity. We conclude that for effective collective migration the RHOA-GEFs/RHOA/actomyosin pathway must be optimally tuned to compromise between generation of motility forces and restriction of intercellular communication.GEFguanine nucleotide exchange factorsGDIguanine dissociation inhibitors16HBEhuman bronchial epithelial cells from the 16HBE14o linePCAprincipal component analysisPCprincipal componentsshRNAsmall hairpin RNAKDknockdownFBSfetal bovine serumPCRpolymerase chain reactionqPCRquantitative PCRROIregion of interest ER -