Group:MUZIC
From Proteopedia
The Z-disc of the muscle sarcomere
Introduction
Although all types of muscle cells use actin and myosin for contraction, only in skeletal and cardiac muscle these proteins are organized into sarcomeric units. They are generally composed of ordered thick (myosin) and thin (actin, tropomyosin, troponin) filaments that slide past each other during contraction. The precise ultra-structural order of these filaments is of utmost importance for converting the molecular interactions produced by actin and myosin in each sarcomere into efficient contraction at the macroscopic level (Figure 1). In addition to those components responsible for active muscle operation, many other filamentous proteins, such as titin and nebulin, have important roles in myofibril structure formation and regulation. Titin, the largest known vertebrate gene product, connects the Z-discs to the central M-band [reviewed in [1]] and nebulin, which spans the length of the actin filaments [reviewed in [2][3][4]]. One of the functionally most complex sub-compartments of the sarcomere is the Z-disc that forms the lateral boundaries between adjacent sarcomeres. This region plays a central role as the site organizing thick filaments and titin into the molecular machinery that is required for muscle contraction and comprises the actin, titin, and nebulin filaments. Thin filaments (actin) from adjacent sarcomeres are anchored at the Z-disc. In this area of the sarcomere, each actin filament overlaps with four filaments from the opposite sarcomere, forming a square lattice, which is cross-connected in a zig-zag pattern by α-actinin-2 [5] (Figure 2). This region plays a central role as the main anchoring point of the molecular machinery for muscle contraction comprising the actin, titin, and nebulin filaments [6][7]. Z-discs are also implicated in mechanosensing and signaling to the nucleus, which contribute to maintenance of muscle homeostasis, and serve as attachment sites for desmin intermediate filaments and often for transverse tubules [reviewed in (Ervasti, 2003), (Gautel, 2011), (Voelkel & Linke, 2011)]. The assembly of the Z-disc is controlled via N-terminal part of titin, which exhibits binding sites for α-actinin-2 as well as to additional Z-disc components. The most striking feature of muscle and Z-disc proteins, in particular, is the diversity of multiple protein-protein interactions that form part of a complex network, involving more than fourty protein (Clark et al, 2002; Frank et al, 2006; Wang et al, 2005) (Figure 3). For example, titin binds to α-actinin-2 via 45-residue sequence motifs, the so-called Z-repeats (Ohtsuka et al, 1997) and dimerizes at its N-terminal through the mediator protein telethonin (Zou et al, 2006).
