PUBLICATION

Pregnancy-associated plasma protein-aa supports hair cell survival by regulating mitochondrial function

Authors
Alassaf, M., Daykin, E.C., Mathiaparanam, J., Wolman, M.A.
ID
ZDB-PUB-190618-2
Date
2019
Source
eLIFE   8: (Journal)
Registered Authors
Wolman, Marc
Keywords
cell biology, neuroscience, zebrafish
MeSH Terms
  • Larva/genetics
  • Larva/metabolism
  • Reactive Oxygen Species/metabolism*
  • Mutation
  • Metalloendopeptidases/genetics
  • Metalloendopeptidases/metabolism
  • Microscopy, Confocal
  • Animals
  • Humans
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Cell Survival/genetics
  • Hair Cells, Auditory/cytology
  • Hair Cells, Auditory/metabolism*
  • Animals, Genetically Modified
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Calcium/metabolism*
  • Mitochondria/genetics
  • Mitochondria/metabolism*
  • Pregnancy-Associated Plasma Protein-A/genetics
  • Pregnancy-Associated Plasma Protein-A/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
(all 24)
PubMed
31205004 Full text @ Elife
Abstract
To support cell survival, mitochondria must balance energy production with oxidative stress. Inner ear hair cells are particularly vulnerable to oxidative stress; thus require tight mitochondrial regulation. We identified a novel molecular regulator of the hair cells' mitochondria and survival: Pregnancy-associated plasma protein-aa (Pappaa). Hair cells in zebrafish pappaa mutants exhibit mitochondrial defects, including elevated mitochondrial calcium, transmembrane potential, and reactive oxygen species (ROS) production and reduced antioxidant expression. In pappaa mutants, hair cell death is enhanced by stimulation of mitochondrial calcium or ROS production and suppressed by a mitochondrial ROS scavenger. As a secreted metalloprotease, Pappaa stimulates extracellular insulin-like growth factor 1 (IGF1) bioavailability. We found that the pappaa mutants' enhanced hair cell loss can be suppressed by stimulation of IGF1 availability and that Pappaa-IGF1 signaling acts post-developmentally to support hair cell survival. These results reveal Pappaa as an extracellular regulator of hair cell survival and essential mitochondrial function.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ml5TgTransgenic Insertion
    p170
      Point Mutation
      s356tTgTransgenic Insertion
        w78TgTransgenic Insertion
          zf243TgTransgenic Insertion
            zf3175TgTransgenic Insertion
              1 - 6 of 6
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              No data available
              Fish
              No data available
              Antibodies
              Name Type Antigen Genes Isotypes Host Organism
              Ab1-myo6polyclonal
                IgGRabbit
                Ab3-sox2polyclonalIgGRabbit
                1 - 2 of 2
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                Orthology
                No data available
                Engineered Foreign Genes
                Marker Marker Type Name
                EGFPEFGEGFP
                GCaMPEFGGCaMP
                GFPEFGGFP
                1 - 3 of 3
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                Mapping
                No data available