The intermediate filament protein peripherin is the specific interaction partner of mouse BPAG1-n (dystonin) in neurons

The dystonia musculorum (dt) mouse suffers from severe degeneration of prim ary sensory neurons. The mutated gene product is named dystonin and is iden tical to the neuronal isoform of bullous pemphigoid antigen 1 (BPAG1-n), BP AG1-n contains an actin-binding domain at its NH2 terminus and a putative i ntermediate filament-binding domain at its COOH terminus. Because the degen erating sensory neurons of dt mice display abnormal accumulations of interm ediate filaments in the axons, BPAG1-n has been postulated to organize the neuronal cytoskeleton by interacting with both the neurofilament triplet pr oteins (NFTPs) and microfilaments. In this paper we show by a variety of me thods that the COOH-terminal tail domain of mouse BPAG1 interacts specifica lly with peripherin, but in contrast: to a previous study (Yang, Y., J. Dow ling, Q.C. Yu, P. Kouklis, D.W, Cleveland, and E. Fuchs. 1996. Cell. 86:655 -665), mouse BPAG1 fails to associate with full-length NFTPs. The tail doma ins interfered with the association of the NFTPs with BPAG1. In dr mice, pe ripherin is present in axonal swellings of degenerating sensory neurons in the dorsal root ganglia and is downregulated even in other neural regions, which have no obvious signs of pathology. Since peripherin and BPAG1-n also display similar expression patterns in the nervous system, we suggest that peripherin is the specific interaction partner of BPAG1-n in vivo.