Plectin–actin complex

The plectin–actin complex is a critical structural and regulatory assembly formed by the interaction of the cytolinker protein plectin with filamentous actin (F-actin) (UniProt P17661). Plectin, a member of the plakin family, utilizes its N-terminal actin-binding domain (ABD) to anchor the actin cytoskeleton to intermediate filaments, microtubules, and various membrane-associated junctional complexes like hemidesmosomes (PubMed: 11483655). This interaction is vital for maintaining the mechanical integrity and viscoelastic properties of tissues, particularly those under high mechanical stress such as skin and muscle (PubMed: 35143044). In pathological contexts, mutations in the PLEC gene that disrupt this complex lead to plectinopathies, most notably epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), characterized by severe skin blistering and progressive muscle weakness (PubMed: 34540018). In oncology, plectin is frequently upregulated and mislocalized to the cell surface (cell surface plectin or CSP), where the plectin–actin complex facilitates cancer cell migration, invasion, and metastasis (PubMed: 34463332). Therapeutic strategies targeting this complex include small molecules like plecstatin-1, which inhibits plectin's cross-linking functions, and monoclonal antibodies like ZB131, which target CSP to disrupt oncogenic signaling and promote anti-tumor immunity (NCT05074472; PubMed: 35143044).

Other names

Plectin-F-actin complexPlectin-microfilament complexPLEC-ACTA complexPlectin-actin interaction

Inhibition of plectin-mediated cytoskeletal cross-linking and stabilization; targeting of cell surface-localized plectin to disrupt oncogenic signaling and induce immune-mediated tumor regression (PubMed: 34463332, NCT05074472).