Practice question

Plectin is a giant cytolinker of the plakin family that simultaneously recognizes actin, microtubules and intermediate filaments, integrating cytoskeletal networks into a cohesive mechanical continuum. Its structure includes an N-terminal actin-binding domain composed of two calponin-homology motifs, a central 200-nm coiled-coil rod dimerization domain, and a C-terminal repeat domain that binds vimentin, keratin, desmin and glial fibrillary acidic protein with distinct isoform specificity. Alternative splicing of first exons targets isoforms to hemidesmosomes via integrin beta4, to focal adhesions, desmosomes, mitochondria and nuclear envelope. At these sites plectin recruits microtubule-associated proteins and directly contacts tubulin, coordinating plus-end dynamics with intermediate filament anchorage. Deletion produces skin blistering with muscular dystrophy due to failure of stress transfer. In contrast spectrin forms tetramers capping actin at membranes, fimbrin bundles actin in microvilli, filamin crosslinks actin orthogonally, none containing high-affinity intermediate filament repeats. Thus plectin alone provides universal bridging activity essential for epithelial and muscle integrity.