A Bpag1 isoform involved in cytoskeletal organization surrounding the nucleus

Bpag1/dystonin proteins are giant cytoskeletal interacting proteins postulated to cross-link cytoskeletal filaments and thereby maintain cellular integrity. Loss of function of non-epithelial Bpag1 isoforms results in neuromuscular dysfunction and early postnatal death in mice. Multiple Bpag1 transcripts have been described, including those encoding protein isoforms that vary at the N-terminal end. Here, we have analyzed the subcellular localizations and cytoskeletal interactions of two isoforms, termed Bpag1a1 and Bpag1a2. We demonstrate that novel sequence at the 5' end of the Bpag1a2 transcript codes for an N-terminal transmembrane domain and targets the protein to the perinuclear region of the cell. Furthermore, we show that the endogenous Bpag1a2 protein is also present in the perinuclear region in myoblast cells. Differences in Bpag1a1 and Bpag1a2 with respect to the extent of their interactions with microtubules and microfilaments are also described, with Bpag1a2 fusion protein serving largely to associate with microfilaments surrounding the nucleus and Golgi apparatus. The overall structure and subcellular localizations of Bpag1a2 indicate possible functions in nuclear envelope structuring, nuclear tethering, and organization of membranous structures surrounding the nucleus