title: V-ATPase proton pumping activity is required for adult zebrafish appendage regeneration.
abstract: The activity of ion channels and transporters generates ion-specific fluxes that encode electrical and/or chemical signals with biological significance. Even though it is long known that some of those signals are crucial for regeneration, only in recent years the corresponding molecular sources started to be identified using mainly invertebrate or larval vertebrate models. We used adult zebrafish caudal fin as a model to investigate which and how ion transporters affect regeneration in an adult vertebrate model. Through the combined use of biophysical and molecular approaches, we show that V-ATPase activity contributes to a regeneration-specific H+ ef`flux. The onset and intensity of both V-ATPase expression and H+ efflux correlate with the different regeneration rate along the proximal-distal axis. Moreover, we show that V-ATPase inhibition impairs regeneration in adult vertebrate. Notably, the activity of this H+ pump is necessary for aldh1a2 and mkp3 expression, blastema cell proliferation and fin innervation. To the best of our knowledge, this is the first report on the role of V-ATPase during adult vertebrate regeneration.
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Monteiro
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Aires
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Becker
authors.affiliation: Centro de Estudos de Doenças Crónicas, Faculdade de Ciências Médicas, Lisboa, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Jacinto
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal; Champalimaud Foundation, Lisboa, Portugal.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Certal
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal; Department de Anatomía Humana, Biología Celular y Zoología, Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Rodríguez-León
mesh_terms: D000671:Amputation, Surgical; D058500:Animal Fins / Q000294:innervation / Q000502:physiology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D007814:Larva / Q000502:physiology; D060172:Morpholinos / Q000494:pharmacology; D017494:Proton Pumps / Q000378:metabolism*; D011522:Protons; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015027:Zebrafish / Q000502:physiology*
chemical_list: D060172:Morpholinos; D017494:Proton Pumps; D011522:Protons; D025262:Vacuolar Proton-Translocating ATPases