PUBLICATION

In Vivo Function of the Chaperonin TRiC in α-Actin Folding during Sarcomere Assembly

Authors
Berger, J., Berger, S., Li, M., Jacoby, A.S., Arner, A., Bavi, N., Stewart, A.G., Currie, P.D.
ID
ZDB-PUB-180111-12
Date
2018
Source
Cell Reports   22: 313-322 (Journal)
Registered Authors
Berger, Joachim, Berger, Silke, Currie, Peter D., Jacoby, Arie, Li, Mei
Keywords
CCT, TRiC, actin, chaperonin, folding, muscle, myofibril, nemaline myopathy, tubulin, zebrafish
MeSH Terms
  • Animals
  • Sarcomeres/metabolism*
  • Zebrafish
  • Actins/metabolism*
  • Humans
  • Chaperonins/chemistry*
  • Chaperonin Containing TCP-1/metabolism*
(all 7)
PubMed
29320728 Full text @ Cell Rep.
Abstract
The TCP-1 ring complex (TRiC) is a multi-subunit group II chaperonin that assists nascent or misfolded proteins to attain their native conformation in an ATP-dependent manner. Functional studies in yeast have suggested that TRiC is an essential and generalized component of the protein-folding machinery of eukaryotic cells. However, TRiC's involvement in specific cellular processes within multicellular organisms is largely unknown because little validation of TRiC function exists in animals. Our in vivo analysis reveals a surprisingly specific role of TRiC in the biogenesis of skeletal muscle α-actin during sarcomere assembly in myofibers. TRiC acts at the sarcomere's Z-disk, where it is required for efficient assembly of actin thin filaments. Binding of ATP specifically by the TRiC subunit Cct5 is required for efficient actin folding in vivo. Furthermore, mutant α-actin isoforms that result in nemaline myopathy in patients obtain their pathogenic conformation via this function of TRiC.
Genes / Markers
Figures
Figure Gallery (10 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-acta1bstandard conditionsProtruding-mouth
WT + MO1-acta1bstandard conditionsProtruding-mouth
WT + MO1-acta1bstandard conditionsProtruding-mouth
WT + MO1-acta1bstandard conditionsProtruding-mouth
WT + MO1-acta1bstandard conditionsProtruding-mouth
cct2hi1269Tg/hi1269Tgstandard conditionsDay 5
cct2hi1269Tg/hi1269Tgstandard conditionsDay 5
cct2hi1269Tg/hi1269Tgstandard conditionsDay 5
cct3sa1761/sa1761standard conditionsProtruding-mouth
cct3sa1761/sa1761standard conditionsProtruding-mouth
1 - 10 of 77
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ed6TgTransgenic Insertion
    hi1269TgTransgenic Insertion
    hi2972bTgTransgenic Insertion
    hi3564TgTransgenic Insertion
    mn30GtTransgenic Insertion
    pc11TgTransgenic Insertion
      pc21TgTransgenic Insertion
        pc22TgTransgenic Insertion
          pc31TgTransgenic Insertion
            pc32TgTransgenic Insertion
              1 - 10 of 17
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              Target Reagent Reagent Type
              acta1bMO1-acta1bMRPHLNO
              cct4CRISPR1-cct4CRISPR
              cct5MO1-cct5MRPHLNO
              cct5MO2-cct5MRPHLNO
              unc45bMO3-unc45bMRPHLNO
              1 - 5 of 5
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              Fish
              Fish
              cct2hi1269Tg/hi1269Tg
              cct3sa1761/sa1761
              cct3sa1761/sa1761; pc22Tg; pc32Tg
              cct4pc34/pc34
              cct4pc34/pc34; pc22Tg; pc32Tg
              cct5hi2972bTg/hi2972bTg
              cct5tf212b/tf212b
              cct5tf212b/tf212b; pc21Tg; pc22Tg
              cct5tf212b/tf212b; pc22Tg; pc32Tg
              cct8mn30Gt/mn30Gt
              1 - 10 of 16
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              Antibodies
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              EGFPEFGEGFP
              GAL4EFGGAL4
              GFPEFGGFP
              mCherryEFGmCherry
              1 - 4 of 4
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              Mapping
              No data available
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              Citation
              Berger, J., Berger, S., Li, M., Jacoby, A.S., Arner, A., Bavi, N., Stewart, A.G., Currie, P.D. (2018) In Vivo Function of the Chaperonin TRiC in α-Actin Folding during Sarcomere Assembly. Cell Reports. 22:313-322.