Cryo-electron tomography of cardiac myofibrils reveals a 3D lattice spring within the Z-discs

Haruaki Yanagisawa,Toshiyuki Oda

doi:10.1038/s42003-020-01321-5

Haruaki Yanagisawa, Toshiyuki Oda

Open Access

https://doi.org/10.1038/s42003-020-01321-5

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Abstract

The Z-disc forms a boundary between sarcomeres, which constitute structural and functional units of striated muscle tissue. Actin filaments from adjacent sarcomeres are cross-bridged by α-actinin in the Z-disc, allowing transmission of tension across the myofibril. Despite decades of studies, the 3D structure of Z-disc has remained elusive due to the limited resolution of conventional electron microscopy. Here, we observed porcine cardiac myofibrils using cryo-electron tomography and reconstructed the 3D structures of the actin-actinin cross-bridging complexes within the Z-discs in relaxed and activated states. We found that the α-actinin dimers showed contraction-dependent swinging and sliding motions in response to a global twist in the F-actin lattice. Our observation suggests that the actin-actinin complex constitutes a molecular lattice spring, which maintains the integrity of the Z-disc during the muscle contraction cycle.

Highlights

The Z-disc forms a boundary between sarcomeres, which constitute structural and functional units of striated muscle tissue
The αactinin monomer has the N-terminal actin-binding domain, which is composed of two calponin homology (CH) domains; the central rod domain, which is composed of four spectrin-like repeats; and the C-terminal tandem EF-hand domains, which are insensitive to calcium in the muscle-type isoforms[3,4,5]
When we carefully examined the previous studies, the reported “small square” lattice is not always square and diamond-shaped “offset-square” lattices have often been reported in mammalian Z-discs[8,9,16]

Summary

Introduction

The Z-disc forms a boundary between sarcomeres, which constitute structural and functional units of striated muscle tissue. Actin filaments from adjacent sarcomeres are cross-bridged by α-actinin in the Z-disc, allowing transmission of tension across the myofibril. We observed porcine cardiac myofibrils using cryo-electron tomography and reconstructed the 3D structures of the actin-actinin cross-bridging complexes within the Z-discs in relaxed and activated states. Our observation suggests that the actin-actinin complex constitutes a molecular lattice spring, which maintains the integrity of the Z-disc during the muscle contraction cycle. In the classical studies of fixed muscle tissues, it has been proposed that the small square and the basket-weave forms represent the relaxed and the active contracted states, respectively[7,11,12]. Under the ion-controlled conditions, we visualized the 3D structural changes within the Z-discs

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