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Maintenance of Melanophore Morphology and Survival Is Cathepsin and vps11 Dependent in Zebrafish

Here, we characterize a Danio rerio zebrafish pigment cell mutant (melanophore integrity mutant), which displays a defect in maintenance of melanophore and iridophore number. Mapping and candidate gene analysis links the melanophore integrity mutant mutation to the vacuolar protein sorting 11 (vps11...

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Autores principales: Clancey, Lauren F., Beirl, Alisha J., Linbo, Tor H., Cooper, Cynthia D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664566/
https://www.ncbi.nlm.nih.gov/pubmed/23724125
http://dx.doi.org/10.1371/journal.pone.0065096
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author Clancey, Lauren F.
Beirl, Alisha J.
Linbo, Tor H.
Cooper, Cynthia D.
author_facet Clancey, Lauren F.
Beirl, Alisha J.
Linbo, Tor H.
Cooper, Cynthia D.
author_sort Clancey, Lauren F.
collection PubMed
description Here, we characterize a Danio rerio zebrafish pigment cell mutant (melanophore integrity mutant), which displays a defect in maintenance of melanophore and iridophore number. Mapping and candidate gene analysis links the melanophore integrity mutant mutation to the vacuolar protein sorting 11 (vps11(w66)) gene. Quantification of vps11(w66) chromatophores during larval stages suggests a decrease in number as compared to wildtype siblings. TUNEL analysis and treatment with the caspase inhibitor, zVAD-fmk, indicate that vps11(w66)chromatophore death is caspase independent. Western blot analysis of PARP-1 cleavage patterns in mutant lysates suggests that increases in pH dependent cathepsin activity is involved in the premature chromatophore death observed in vps11(w66) mutants. Consistently, treatment with ALLM and Bafilomycin A1 (cathepsin/calpain and vacuolar-type H+-ATPase inhibitors, respectively), restore normal melanophore morphology and number in vps11(w66) mutants. Last, LC3B western blot analysis indicates an increase in autophagosome marker, LC3B II in vps11(w66) mutants as compared to wildtype control, but not in ALLM or Bafilomycin A1 treated mutants. Taken together, these data suggest that vps11 promotes normal melanophore morphology and survival by inhibiting cathepsin release and/or activity.
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spelling pubmed-36645662013-05-30 Maintenance of Melanophore Morphology and Survival Is Cathepsin and vps11 Dependent in Zebrafish Clancey, Lauren F. Beirl, Alisha J. Linbo, Tor H. Cooper, Cynthia D. PLoS One Research Article Here, we characterize a Danio rerio zebrafish pigment cell mutant (melanophore integrity mutant), which displays a defect in maintenance of melanophore and iridophore number. Mapping and candidate gene analysis links the melanophore integrity mutant mutation to the vacuolar protein sorting 11 (vps11(w66)) gene. Quantification of vps11(w66) chromatophores during larval stages suggests a decrease in number as compared to wildtype siblings. TUNEL analysis and treatment with the caspase inhibitor, zVAD-fmk, indicate that vps11(w66)chromatophore death is caspase independent. Western blot analysis of PARP-1 cleavage patterns in mutant lysates suggests that increases in pH dependent cathepsin activity is involved in the premature chromatophore death observed in vps11(w66) mutants. Consistently, treatment with ALLM and Bafilomycin A1 (cathepsin/calpain and vacuolar-type H+-ATPase inhibitors, respectively), restore normal melanophore morphology and number in vps11(w66) mutants. Last, LC3B western blot analysis indicates an increase in autophagosome marker, LC3B II in vps11(w66) mutants as compared to wildtype control, but not in ALLM or Bafilomycin A1 treated mutants. Taken together, these data suggest that vps11 promotes normal melanophore morphology and survival by inhibiting cathepsin release and/or activity. Public Library of Science 2013-05-27 /pmc/articles/PMC3664566/ /pubmed/23724125 http://dx.doi.org/10.1371/journal.pone.0065096 Text en © 2013 Clancey et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Clancey, Lauren F.
Beirl, Alisha J.
Linbo, Tor H.
Cooper, Cynthia D.
Maintenance of Melanophore Morphology and Survival Is Cathepsin and vps11 Dependent in Zebrafish
title Maintenance of Melanophore Morphology and Survival Is Cathepsin and vps11 Dependent in Zebrafish
title_full Maintenance of Melanophore Morphology and Survival Is Cathepsin and vps11 Dependent in Zebrafish
title_fullStr Maintenance of Melanophore Morphology and Survival Is Cathepsin and vps11 Dependent in Zebrafish
title_full_unstemmed Maintenance of Melanophore Morphology and Survival Is Cathepsin and vps11 Dependent in Zebrafish
title_short Maintenance of Melanophore Morphology and Survival Is Cathepsin and vps11 Dependent in Zebrafish
title_sort maintenance of melanophore morphology and survival is cathepsin and vps11 dependent in zebrafish
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664566/
https://www.ncbi.nlm.nih.gov/pubmed/23724125
http://dx.doi.org/10.1371/journal.pone.0065096
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