Young Kevin G, Pinheiro Bruno, Kothary Rashmi
Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6.
Exp Cell Res. 2006 Jan 15;312(2):121-34. doi: 10.1016/j.yexcr.2005.10.002. Epub 2005 Nov 9.
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.
Bpag1/张力蛋白是一种巨大的细胞骨架相互作用蛋白，推测其可交联细胞骨架细丝，从而维持细胞完整性。非上皮Bpag1亚型功能丧失会导致小鼠出现神经肌肉功能障碍和出生后早期死亡。已描述了多种Bpag1转录本，包括那些编码在N端不同的蛋白质亚型的转录本。在此，我们分析了两种亚型Bpag1a1和Bpag1a2的亚细胞定位和细胞骨架相互作用。我们证明，Bpag1a2转录本5'端的新序列编码一个N端跨膜结构域，并将该蛋白靶向到细胞的核周区域。此外，我们表明内源性Bpag1a2蛋白也存在于成肌细胞的核周区域。还描述了Bpag1a1和Bpag1a2在与微管和微丝相互作用程度方面的差异，Bpag1a2融合蛋白主要与围绕细胞核和高尔基体的微丝相关联。Bpag1a2的整体结构和亚细胞定位表明其在核膜构建、核系留以及围绕细胞核的膜结构组织方面可能具有功能。
