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

Publication date: 9 January 2018
Source:Cell Reports, Volume 22, Issue 2
Author(s): Joachim Berger, Silke Berger, Mei Li, Arie S. Jacoby, Anders Arner, Navid Bavi, Alastair G. Stewart, Peter D. Currie
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.

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Teaser

TRiC-deficient zebrafish feature specific defects in sarcomere and neurite formation. Berger et al. demonstrate a role for TRiC as a multiprotein scaffold positioned at the sarcomere's Z-disk, where it enhances the processing of skeletal muscle α-actin. Accordingly, TRiC causes aggregation of myopathic α-actin variants in nemaline myopathy.


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