Maintenance of melanophore morphology and survival is cathepsin and vps11 dependent in zebrafish

Lauren F Clancey; Alisha J Beirl; Tor H Linbo; Cynthia D Cooper

doi:10.1371/journal.pone.0065096

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Maintenance of melanophore morphology and survival is cathepsin and vps11 dependent in zebrafish

Journal article

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Maintenance of melanophore morphology and survival is cathepsin and vps11 dependent in zebrafish

Lauren F Clancey, Alisha J Beirl, Tor H Linbo and Cynthia D Cooper

PloS one, Vol.8(5), pp.e65096-e65096

2013

DOI: https://doi.org/10.1371/journal.pone.0065096

Handle:

https://hdl.handle.net/2376/103986

PMCID: PMC3664566

PMID: 23724125

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Abstract

Melanophores - metabolism

Vesicular Transport Proteins - metabolism

Cell Survival - genetics

Autophagy - drug effects

Organ Specificity - genetics

Caspases - metabolism

Macrolides - pharmacology

Autophagy - genetics

Chromosomes

Cell Survival - drug effects

Zebrafish Proteins - metabolism

Vesicular Transport Proteins - genetics

Enzyme Inhibitors - pharmacology

Gene Expression Regulation

Chromosome Mapping

Enzyme Activation - drug effects

Melanophores - cytology

Zebrafish - genetics

Animals

Cathepsins - genetics

Cathepsins - metabolism

Zebrafish - metabolism

Melanophores - drug effects

Mutation

Zebrafish Proteins - genetics

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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Title: Maintenance of melanophore morphology and survival is cathepsin and vps11 dependent in zebrafish
Creators: Lauren F Clancey - School of Molecular Biosciences, Washington State University Vancouver, Vancouver, Washington, United States of America
Alisha J Beirl
Tor H Linbo
Cynthia D Cooper
Publication Details: PloS one, Vol.8(5), pp.e65096-e65096
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Identifiers: 99900546989701842
Language: English
Resource Type: Journal article