A schematic model of the cytoskeletal filament linkages at the sarcolemma of striated muscle. Four major cytoskeletal/membrane junctions are depicted: (a) cadherin-based linkages to actin and intermediate filaments (desmin); (b) integrin-based focal adhesions; (c) dystroglycan complex (DGC); and (d) spectrin-based membrane cytoskeleton. The cadherin-based fascia adheren at the intercalated disc couples neighboring cardiomyocytes (through homotypic interactions) and tethers the contractile apparatus to the muscle termini. Desmosomes are a second cadherin-based junction that anchor desmin filaments at the intercalated disc. Connections between intermediate filament proteins and the membrane may occur through a plectin/{alpha}ß-crystallin complex or via an association with DGC via dystrobrevin. Integrin-based focal adhesions and the DGC act as transmembrane receptors for ECM components (e.g., laminin) and link the extracellular surface with the actin cytoskeleton. Integrins associate with talin, {alpha}-actinin, vinculin and N-RAP to form a strong mechanical link to actin filaments. Integrins could directly interact with {alpha}-actinin and/or other components not depicted here to mediate a connection with actin. The DGC consists of the transmembrane complex {alpha}/ß-dystroglycan, dystrophin, the sarcoglycans, and other components not depicted here. Spectrin is enriched at costameres, and is an important component of the membrane cytoskeleton. It is linked to the membrane through ankyrin and probably the Na,K-ATPase transmembrane protein. Spectrin may have an additional role in anchoring the contractile apparatus to the membrane though an interaction with MLP. Importantly, all of these linkage complexes can bind to the submembraneous actin ({gamma}-actin) and are probably interlinked through this association as well as other unknown interactions.