Toll receptors remodel epithelia by directing planar-polarized Src and PI3K activity

Toll-like receptors are essential for animal development and survival, with conserved roles in innate immunity, tissue patterning, and cell behavior. The mechanisms by which Toll receptors signal to the nucleus are well characterized, but how Toll receptors generate rapid, localized signals at the cell membrane to produce acute changes in cell polarity and behavior is not known. We show that Drosophila Toll receptors direct epithelial convergent extension by inducing planar-polarized patterns of Src and PI3-kinase (PI3K) activity. Toll receptors target Src activity to specific sites at the membrane, and Src recruits PI3K to the Toll-2 complex through tyrosine phosphorylation of the Toll-2 cytoplasmic domain. Reducing Src or PI3K activity disrupts planar-polarized myosin assembly, cell intercalation, and convergent extension, whereas constitutive Src activity promotes ectopic PI3K and myosin cortical localization. These results demonstrate that Toll receptors direct cell polarity and behavior by locally mobilizing Src and PI3K activity. [Display omitted] •Toll receptors generate planar-polarized patterns of Src and PI3K activity•Src and PI3K are required for localized myosin contractility and convergent extension•Src kinases promote Toll-2 phosphorylation and Toll-2/PI3K-reg complex formation•Toll-2 phosphorylation is necessary for planar polarity and convergent extension Toll receptors provide critical spatial cues that drive cell movements during convergent extension. Tamada and Shi et al. show that Toll receptors organize cell movements by generating planar-polarized patterns of Src and PI3K activity. Toll-2 tyrosine phosphorylation recruits PI3K to the Toll-2 complex, promoting localized myosin assembly and cell rearrangement.