V-ATPase proton pumping activity is required for adult zebrafish appendage regeneration

• Published in: PloS one Vol. 9; no. 3; p. e92594
• Main Authors: Monteiro, Joana, Aires, Rita, Becker, Jörg D, Jacinto, António, Certal, Ana C, Rodríguez-León, Joaquín
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.03.2014; Public Library of Science (PLoS)
• Subjects: Adenosine triphosphatase; Amputation; Animal Fins - innervation; Animal Fins - physiology; Animals; Apoptosis; ATPases; Biology and Life Sciences; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Danio rerio; Efflux; Fluxes; Gene Knockdown Techniques; H+-transporting ATPase; Hydrogen; Innervation; Ion channels; Larva - physiology; Melanoma; Morpholinos - pharmacology; Proton Pumps - metabolism; Protons; Regeneration; Regeneration - drug effects; Regeneration - physiology; Research and Analysis Methods; Up-Regulation - drug effects; Vacuolar Proton-Translocating ATPases - antagonists & inhibitors; Vacuolar Proton-Translocating ATPases - metabolism; Wound healing; Xenopus; Zebrafish; Zebrafish - physiology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0092594

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.