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.