AN ESSENTIAL CYTOSKELETAL LINKER PROTEIN CONNECTING ACTIN MICROFILAMENTS TO INTERMEDIATE FILAMENTS

Typified by rapid degeneration of sensory neurons, dystonia musculorum mice have a defective BPAG1 gene, known to be expressed in epidermis. We report a neuronal splice form, BPAG1n, which localizes to sensory axons. Both isoforms have a coiled-coil rod, followed by a carboxy dom ain that associates with intermediate filaments. However, the amino te rminus of BPAG1n differs from BPAG1e in that it contains a functional actin-binding domain. In transfected cells, BPAG1n coaligns neurofilam ents and microfilaments, establishing this as a cytoskeletal protein i nterconnecting actin and intermediate filament cytoskeletons. In BPAG1 null mice, axonal architecture is markedly perturbed, consistent with a failure to tether neurofilaments to the actin cytoskeleton and unde rscoring the physiological relevance of this protein.