School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, China.
Department of Basic Sciences and Craniofacial Biology, College of Dentistry, New York University, NY, USA.
FEBS J. 2020 Oct;287(20):4500-4524. doi: 10.1111/febs.15249. Epub 2020 Mar 5.
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-prolyl cis-trans isomerase 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.
有证据表明，无机多聚磷酸盐（polyP）是一种广泛参与多种生物过程的基本分子。在高等真核生物中，多聚磷酸盐在成骨细胞中含量丰富，但它的功能仍存在疑问。在这里，我们发现多聚磷酸盐在内质网（ER）中特别丰富，在成骨细胞 SaOS-2 模型细胞系中，它与亲环素 B（CypB）共定位。多聚磷酸盐直接且特异性地与 CypB 结合，抑制其肽基脯氨酰顺反异构酶活性，该活性对胶原蛋白折叠至关重要。多聚精胺对多聚磷酸盐的螯合作用和细胞中多聚磷酸酶表达对 ER 中多聚磷酸盐的特异性减少均降低了胶原蛋白的错误折叠，并证实内源性多聚磷酸盐作为 CypB 介导的胶原蛋白折叠的分子控制因子发挥作用。我们提出，多聚磷酸盐是内质网中蛋白质平衡的一个以前未被认识的关键调节剂。
