Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada.
Front Biosci (Landmark Ed). 2011 Jan 1;16(4):1505-16. doi: 10.2741/3801.
The SPRN gene encodes the Shadoo glycoprotein (Sho), a central nervous system-expressed member of the prion protein superfamily. Sho has similarity to two features within PrPC's natively unstructured N-terminus, a hydrophobic domain and tandem repeats with positively charged residues. Indeed, scrutiny of Sho's biochemical properties in uninfected cells has revealed overlaps with the properties of PrPC, these including shared protein binding partners. SPRN is conserved in mammals, as is the prion gene PRNP, but in sheep SPRN and PRNP are both marked by polymorphic variation, suggestive of a shared selection pressure within these scrapie disease-prone livestock animals. In rodent models of prion disease there are reduced levels of Sho in infected tissues, defining a form of cross-regulation between full-length Sho holoprotein and PrPSc. In human prion disease an SPRN signal peptide polymorphism is associated with risk for sporadic Creutzfeldt-Jakob Disease (CJD), while two patients with early-onset variant CJD carried putatively inactive SPRN alleles. Further investigation of Sho as a novel tracer or modifier for the accumulation of pathologic forms of PrP may prove advantageous.
SPRN 基因编码 Shadoo 糖蛋白（Sho），它是朊病毒蛋白超家族中在中枢神经系统中表达的成员。Sho 与 PrPC 的天然无结构 N 端的两个特征具有相似性，即疏水区和带正电荷的重复序列。事实上，在未感染细胞中对 Sho 的生化特性进行仔细检查后发现，它与 PrPC 的特性重叠，包括共享的蛋白质结合伴侣。SPRN 在哺乳动物中是保守的，PrNP 也是如此，但在绵羊中，SPRN 和 PRNP 都存在多态性变异，表明在这些易患羊瘙痒病的牲畜中存在共同的选择压力。在朊病毒疾病的啮齿动物模型中，感染组织中的 Sho 水平降低，这定义了全长 Sho 完整蛋白和 PrPSc 之间的一种交叉调节形式。在人类朊病毒疾病中，SPRN 信号肽多态性与散发性克雅氏病（CJD）的风险相关，而两名早发性变异 CJD 患者携带推定无活性的 SPRN 等位基因。进一步研究 Sho 作为病理性 PrP 积累的新型示踪剂或调节剂可能会证明是有利的。
