Inorganic polyphosphate controls cyclophilin B-mediated collagen folding in osteoblast-like cells.
Inorganic polyphosphate controls cyclophilin B-mediated collagen folding in osteoblast-like cells.
复制标题
无机多磷酸盐控制成骨细胞样细胞中亲环蛋白 B 介导的胶原蛋白折叠。
DOI：
10.1111/febs.15249
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Tanner,JulianA
中科院分区：
文献类型：
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作者：
Khong,MeiLi;Li,Lina;Solesio,MariaE;Pavlov,EvgenyV;Tanner,JulianA
越来越多的证据表明，无机聚磷酸盐(Polyp)是一种参与广泛生物过程的基本分子。在高等真核生物中，息肉在成骨细胞中含量丰富，但其功能仍存在疑问。在这里，我们发现息肉在内质网(ER)中特别丰富，在那里它与成骨细胞SAOS-2模型细胞系中的亲环素B(CypB)共存。息肉直接与CypB特异性结合，抑制其对胶原折叠至关重要的肽基-脯氨基顺式转移酶活性。精胺对息肉的封存和内质网特异性息肉通过多聚磷酸酶的表达减少了胶原的错误折叠，证实了内源性息肉对CypB介导的胶原折叠起着分子控制作用。我们认为息肉是内质网中蛋白质动态平衡的关键调节因子。
Evidence is emerging that inorganic polyphosphate (polyP) is a fundamental molecule involved in a wide range of biological processes. In higher eukaryotes, polyP is abundant in osteoblasts but questions remain as to its functions. Here, we find that polyP is particularly enriched in endoplasmic reticulum (ER) where it colocalizes with cyclophilin B (CypB) using osteoblastic SaOS‐2 model cell line. PolyP binds directly and specifically to CypB, inhibiting its peptidyl‐prolylcis‐transisomerase activity which is critical for collagen folding. PolyP sequestration by spermine and ER‐specific polyP reduction by polyphosphatase expression in cells reduced collagen misfolding and confirmed that endogenous polyP acts as a molecular control of CypB‐mediated collagen folding. We propose that polyP is a previously unrecognized critical regulator of protein homeostasis in ER.