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
-
- Actins/metabolism*
- Animals
- Chaperonin Containing TCP-1/metabolism*
- Chaperonins/chemistry*
- Humans
- Sarcomeres/metabolism*
- Zebrafish
- PubMed
- 29320728 Full text @ Cell Rep.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping