title: ERK and phosphoinositide 3-kinase temporally coordinate different modes of actin-based motility during embryonic wound healing.
abstract: Embryonic wound healing provides a perfect example of efficient recovery of tissue integrity and homeostasis, which is vital for survival. Tissue movement in embryonic wound healing requires two functionally distinct actin structures: a contractile actomyosin cable and actin protrusions at the leading edge. Here, we report that the discrete formation and function of these two structures is achieved by the temporal segregation of two intracellular upstream signals and distinct downstream targets. The sequential activation of ERK and phosphoinositide 3-kinase (PI3K) signalling divides Xenopus embryonic wound healing into two phases. In the first phase, activated ERK suppresses PI3K activity, and is responsible for the activation of Rho and myosin-2, which drives actomyosin cable formation and constriction. The second phase is dominated by restored PI3K signalling, which enhances Rac and Cdc42 activity, leading to the formation of actin protrusions that drive migration and zippering. These findings reveal a new mechanism for coordinating different modes of actin-based motility in a complex tissue setting, namely embryonic wound healing.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Siwei
authors.initials: S
authors.lastname: Zhang
authors.forename: Ximena
authors.initials: X
authors.lastname: Soto
authors.forename: Sarah
authors.initials: S
authors.lastname: Woolner
authors.forename: Enrique
authors.initials: E
authors.lastname: Amaya
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D014945:Wound Healing; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology*
chemical_list: D000199:Actins; D029867:Xenopus Proteins; D019869:Phosphatidylinositol 3-Kinases
keywords: ERK; PI3K; Rho GTPases; Wound healing; Xenopus