Abstract
Extracellular signals regulate epithelial homeostasis, cell fate and the patterning of cell behaviors during embryogenesis, wound healing, regeneration and disease progression. Previous studies in our group found that cell lysate from intentionally wounded Xenopus laevis embryos triggers a strong but transient contraction in neighboring epithelia, whether contiguous to the wound site or in non-wounded embryos. We previously identified extracellular ATP (eATP) as a possible candidate signal. Here we test additional candidates and find that several nucleotides, including ADP, UTP and UDP, also trigger contractility. Through a temporal and spatial screen of lysate activity, an inhibitor screen and morpholino knockdown of candidate receptors, we find that contractility is mediated by a G-protein-coupled purinergic receptor, P2Y2 (P2RY2). Activated P2RY2 triggers F-actin assembly and myosin II contractility. Knockdown of P2RY2 or overexpression of mutant G protein effectors abrogate epithelial contractility when epithelia are exposed to eATP or lysate. We demonstrate that the major contributors to epithelial contractility in lysate are the extracellular nucleotide triphosphates ATP and UTP, which are sensed by P2RY2 and transduced through G proteins to contract the epithelium.