The sarcomeric structure and its junction with the plasma membrane. The contractile unit lies between two Z-discs. The titin molecule (green), extending from a Z-disc to the M-line, holds the actin (blu and yellow bars) and myosin (brown) filaments in longitudinal frame. The M-line and the Z-discs are protein scaffolds, orientating myosin and actin filaments, respectively. The boxed area is magnified to illustrate the junctional complex connecting the Z-disc structure to integrins at the plasma membrane. The Z-disc is a supramolecular complex, organizing actin filaments in parallel arrays. a-actinin plays a central role in the Z-disc structure, binding both actin and MLP, T-cap, titin. At the same time, a-actinin connects to vinculin and talin, which directly bind to the distal region of the β1D integrin cytoplasmic domain. The extracellular region of the integrin heterodimer binds to laminin in the basement membrane, thus allowing propagation of the stretching and shortening of the contractile filaments to the plasma membrane and the associated basal lamina along the longitudinal axis of the cell. Such a junctional structure is known as a costamere. Several additional molecules also present in this structure have been omitted for the sake of simplicity, even though they are likely to play a crucial role. Abbreviations: MLP, muscle LIM domain protein; T-cap, titin-cap.

 

 

Melusin acts as an integrin-linked biomechanical sensor binding to the β1 integrin cytoplasmic region at costameres.