An efficient delivery of DAMPs on the cell surface by the unconventional secretion pathway.
An efficient delivery of DAMPs on the cell surface by the unconventional secretion pathway.
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DOI：
10.1016/j.bbrc.2010.12.061
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发表时间：
2011-01
影响因子：
3.1
通讯作者：
Haiyan Zhu;Lan Wang;Yuanyuan Ruan;Lei Zhou;Dongmei Zhang;Z. Min;Jianhui Xie;Min Yu;J. Gu
中科院分区：
文献类型：
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作者：
Haiyan Zhu;Lan Wang;Yuanyuan Ruan;Lei Zhou;Dongmei Zhang;Z. Min;Jianhui Xie;Min Yu;J. Gu
损伤相关分子模式（DAMP）是从死亡细胞释放的信号，在几种炎症性疾病中引起免疫系统反应。在正常情况下，许多DAMP是具有确定的细胞内功能的核蛋白或胞质蛋白，但它们可以在组织损伤后在细胞表面上被发现。易位的DAMP的生物学功能仍然不是很清楚，需要这些分子在细胞表面上的有效递送来阐明它们的生物学效应。在这项研究中，我们证明了一种非经典的分泌信号肽，HASPB的N-末端18个氨基酸（HASPB-N18），可以有效地将Hsp 60，Hsp 70和HMGB 1传递到细胞表面。此外，通过HASPB-N18在细胞表面上递送这些分子不限于特定的细胞系，因为几种细胞系可以使用这种递送信号将这些分子递送到细胞表面上。此外，我们证明了HASPB-N18递送的细胞表面上的Hsp 60可以被可溶性形式的LOX-1识别，这意味着HASPB-N18递送的细胞表面上的DAMP在转运过程中具有适当的构象。因此，通过HASPB-N18递送DAMP是进一步理解DAMP在细胞表面上的生物学意义的可靠模型。
Damage-associated molecular patterns (DAMPs) are signals released from dying cells evoking the immune system response in several inflammatory disorders. In normal situations, many of DAMPs are nuclear or cytosolic proteins with defined intracellular function, but they could be found on the cell surface following tissue injury. The biological function of the translocated DAMPs is still not well known and an efficient delivery of these molecules on the cell surface is required to clarify their biological effects. In this study, we demonstrated that an unclassical secretory signal peptide, N-terminal 18 amino acids of HASPB (HASPB-N18), could efficiently deliver Hsp60, Hsp70, and HMGB1 on the cell surface. Furthermore, the delivery of these molecules on the cell surface by HASPB-N18 is not limited to a special cell line because several cell lines could use this delivery signal to deliver these molecules on the cell surface. Moreover, we demonstrated that Hsp60 on the cell surface delivered by HASPB-N18 could be recognized by a soluble form of LOX-1, which implies that DAMPs on the cell surface delivered by HASPB-N18 have a proper conformation during transport. Therefore, delivery of DAMPs by HASPB-N18 is a reliable model to further understand the biological significance of DAMPs on the cell surface.