Supracellular contractility in Xenopus laevis embryonic epithelia regulated by extracellular nucleotides and the purinergic G-protein coupled receptor P2Y2.

Extracellular signals regulate epithelial homeostasis, cell fate and pattern cell behaviors during embryogenesis, wound healing, regeneration, and disease progression. Previous studies in our group found cell lysate from intentionally wounded 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. Here we test additional candidates and find several nucleotides including ADP, UTP, and UDP also trigger contractility. Through a temporal and spatial screen of lysate activity, an inhibitor screen, and morpholino knock-down of candidate receptors, we find 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 extracellular nucleotide triphosphates ATP and UTP, which are sensed by P2RY2 and transduced through G-proteins to contract the epithelium. Summary StatementContractility of the Xenopus embryonic epithelium can be driven by extracellular nucleotides ATP or UTP and actuated by the G-protein coupled purinergic receptor P2Y2 (P2RY2). HighlightsO_LIExtracellular nucleotides ATP and UTP can trigger epithelial contractility. C_LIO_LIEpithelia contract in response to (ATP [~] UTP) > (ADP [~] UDP) > ADO (adenosine). C_LIO_LIThe purinergic G-protein coupled receptor P2Y2 is responsible for this contractile response by indirectly modulating actomyosin contractility. C_LI