The mitotic spindle protein SPAG5/Astrin connects to the Usher protein network postmitotically.
The mitotic spindle protein SPAG5/Astrin connects to the Usher protein network postmitotically.
复制标题
有丝分裂纺锤体蛋白Spag5/Astrin在森林膜上连接到Usher蛋白网络。
作者：
Kersten FF;van Wijk E;Hetterschijt L;Bauβ K;Peters TA;Aslanyan MG;van der Zwaag B;Wolfrum U;Keunen JE;Roepman R;Kremer H
Usher综合征2A （USH2A）基因突变是导致非综合征性视网膜色素变性和Usher综合征的原因，Usher综合征是合并聋盲的最常见原因。为了深入了解USH2A相关视网膜变性的分子病理学，我们旨在鉴定视网膜中USH2A异构体B （USH2AisoB）的相互作用蛋白。我们在视网膜中发现了中心体和微管相关蛋白精子相关抗原（SPAG）5。SPAG5还被发现与另一个先前描述的USH2AisoB相互作用伙伴相互作用：中心体9 - in样蛋白NINLisoB。通过原位杂交，我们发现Spag5在小鼠胚胎发育过程中广泛表达，在眼、耳蜗、脑、肾和肝中都有明显的信号。定量PCR检测SPAG5在成人组织中的表达，在视网膜、脑、肠、肾和睾丸中均有表达。在视网膜中，Spag5、Ush2aisoB和NinlisoB存在于感光细胞的几个亚细胞结构中，并共定位于基底。基于这些结果和USH蛋白在囊泡运输中的作用，以及为内耳和视网膜提供结构支持，我们假设SPAG5、USH2AisoB和NINLisoB可能共同参与基于微管的细胞质运输蛋白质，这些蛋白质对纤毛的形成、维持和/或功能至关重要。
Mutations in the gene for Usher syndrome 2A (USH2A) are causative for non-syndromic retinitis pigmentosa and Usher syndrome, a condition that is the most common cause of combined deaf-blindness. To gain insight into the molecular pathology underlying USH2A-associated retinal degeneration, we aimed to identify interacting proteins of USH2A isoform B (USH2AisoB) in the retina. We identified the centrosomal and microtubule-associated protein sperm-associated antigen (SPAG)5 in the retina. SPAG5 was also found to interact with another previously described USH2AisoB interaction partner: the centrosomal ninein-like protein NINLisoB. Using In situ hybridization, we found that Spag5 was widely expressed during murine embryonic development, with prominent signals in the eye, cochlea, brain, kidney and liver. SPAG5 expression in adult human tissues was detected by quantitative PCR, which identified expression in the retina, brain, intestine, kidney and testis. In the retina, Spag5, Ush2aisoB and NinlisoB were present at several subcellular structures of photoreceptor cells, and colocalized at the basal bodies. Based on these results and on the suggested roles for USH proteins in vesicle transport and providing structural support to both the inner ear and the retina, we hypothesize that SPAG5, USH2AisoB and NINLisoB may function together in microtubule-based cytoplasmic trafficking of proteins that are essential for cilium formation, maintenance and/or function.