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 domain that associates with intermediate filaments. However, the amino terminus of BPAG1n differs from BPAG1e in that it contains a functional actin-binding domain. In transfected cells, BPAG1n coaligns neurofilaments and microfilaments, establishing this as a cytoskeletal protein interconnecting 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 underscoring the physiological relevance of this protein.
Yang
Y
Y
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Illinois 60637, USA.
Dowling
J
J
Yu
Q C
QC
Kouklis
P
P
Cleveland
D W
DW
Fuchs
E
E
D008841:Actin Cytoskeleton / Q000737:chemistry*; D017398:Alternative Splicing; D000818:Animals; D001324:Autoantigens / Q000502:physiology*; D001923:Brain Chemistry; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000648:ultrastructure; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D007382:Intermediate Filaments / Q000737:chemistry*; D051379:Mice; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins / Q000502:physiology*; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D016900:Neurofilament Proteins / Q000378:metabolism*; D009475:Neurons, Afferent / Q000648:ultrastructure*; D024041:Non-Fibrillar Collagens; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D013116:Spinal Cord / Q000737:chemistry; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D024041:Non-Fibrillar Collagens; D012333:RNA, Messenger; D000097805:Collagen Type XVII; C486268:DST protein, human; C095667:Dst protein, mouse