Polyphosphate: A Conserved Modifier of Amyloidogenic Processes.
Polyphosphate: A Conserved Modifier of Amyloidogenic Processes.
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DOI：
10.1016/j.molcel.2016.07.016
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发表时间：
2016-09-01
期刊：
影响因子：
16
通讯作者：
Jakob U
中科院分区：
文献类型：
--
作者：
Cremers CM;Knoefler D;Gates S;Martin N;Dahl JU;Lempart J;Xie L;Chapman MR;Galvan V;Southworth DR;Jakob U
聚磷酸盐（polyP）是一种具有数十亿年历史的生物聚合物，在所研究的每个细胞、组织和生物体中产生。聚P结构极其简单，由共价连接的无机磷酸盐基团的长链组成。我们在这里报告了一个令人惊讶的发现，即聚P在加速淀粉样纤维形成方面显示出显著的功效。我们发现polyP作为各种不同淀粉样蛋白的有效成核源，从细菌CsgA到人α-突触核蛋白，Aβ1-40/42和Tau。与在不存在聚P的情况下形成的原纤维相比，聚P相关的α-突触核蛋白原纤维在接种行为、形态和原纤维稳定性方面显示出明显的差异。在体内，聚P的淀粉样蛋白刺激和纤维稳定作用具有广泛的影响，增加了病原菌中生物膜形成的速率，减轻了分化的神经母细胞瘤细胞和C.作为人类折叠疾病模型的线虫菌株。这些结果表明，我们已经发现了一个保守的细胞保护性修饰淀粉样蛋白的过程。
Polyphosphate (polyP), a several billion year old biopolymer, is produced in every cell, tissue, and organism studied. Structurally extremely simple, polyP consists of long chains of covalently linked inorganic phosphate groups. We report here the surprising discovery that polyP shows a remarkable efficacy in accelerating amyloid fibril formation. We found that polyP serves as an effective nucleation source for various different amyloid proteins, ranging from bacterial CsgA to human α-Synuclein, Aβ1-40/42 and Tau. PolyP-associated α-Synuclein fibrils show distinct differences in seeding behavior, morphology and fibril stability compared to fibrils formed in the absence of polyP. In vivo, the amyloid-stimulating and fibril-stabilizing effects of polyP have wide-reaching consequences, increasing the rate of biofilm formation in pathogenic bacteria and mitigating amyloid toxicity in differentiated neuroblastoma cells and C. elegans strains that serve as models for human folding diseases. These results suggest that we have discovered a conserved cytoprotective modifier of amyloidogenic processes.