PUBLICATION

Mob4-dependent STRIPAK involves the chaperonin TRiC to coordinate myofibril and microtubule network growth

Authors
Berger, J., Berger, S., Currie, P.D.
ID
ZDB-PUB-220624-17
Date
2022
Source
PLoS Genetics   18: e1010287 (Journal)
Registered Authors
Berger, Joachim, Berger, Silke, Currie, Peter D.
Keywords
none
MeSH Terms
  • Actins/genetics
  • Actins/metabolism
  • Animals
  • Sarcomeres/metabolism
  • Zebrafish*/genetics
  • Myofibrils*/metabolism
  • Chaperonins/metabolism
  • Microtubules/genetics
(all 8)
PubMed
35737712 Full text @ PLoS Genet.
Abstract
Myofibrils of the skeletal muscle are comprised of sarcomeres that generate force by contraction when myosin-rich thick filaments slide past actin-based thin filaments. Surprisingly little is known about the molecular processes that guide sarcomere assembly in vivo, despite deficits within this process being a major cause of human disease. To overcome this knowledge gap, we undertook a forward genetic screen coupled with reverse genetics to identify genes required for vertebrate sarcomere assembly. In this screen, we identified a zebrafish mutant with a nonsense mutation in mob4. In Drosophila, mob4 has been reported to play a role in spindle focusing as well as neurite branching and in planarians mob4 was implemented in body size regulation. In contrast, zebrafish mob4geh mutants are characterised by an impaired actin biogenesis resulting in sarcomere defects. Whereas loss of mob4 leads to a reduction in the amount of myofibril, transgenic expression of mob4 triggers an increase. Further genetic analysis revealed the interaction of Mob4 with the actin-folding chaperonin TRiC, suggesting that Mob4 impacts on TRiC to control actin biogenesis and thus myofibril growth. Additionally, mob4geh features a defective microtubule network, which is in-line with tubulin being the second main folding substrate of TRiC. We also detected similar characteristics for strn3-deficient mutants, which confirmed Mob4 as a core component of STRIPAK and surprisingly implicates a role of the STRIPAK complex in sarcomerogenesis.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
pc21TgTransgenic Insertion
    pc22TgTransgenic Insertion
      pc43
        Point Mutation
        pc44
          Small Deletion
          pc45
            Indel
            pc46TgTransgenic Insertion
              pc47TgTransgenic Insertion
                rw021TgTransgenic Insertion
                  sa1761
                    Point Mutation
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Target Reagent Reagent Type
                    mob4CRISPR1-mob4CRISPR
                    mob4MO1-mob4MRPHLNO
                    mob4MO2-mob4MRPHLNO
                    strn3CRISPR1-strn3CRISPR
                    strn3CRISPR2-strn3CRISPR
                    1 - 5 of 5
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                    Fish
                    Antibodies
                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    EGFPEFGEGFP
                    GFPEFGGFP
                    mCherryEFGmCherry
                    1 - 3 of 3
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                    Mapping
                    No data available