Mechanisms for Hsp70 secretion: Crossing membranes without a leader
Mechanisms for Hsp70 secretion: Crossing membranes without a leader
复制标题
DOI：
10.1016/j.ymeth.2007.06.009
复制
发表时间：
2007-11-01
期刊：
影响因子：
4.8
通讯作者：
Calderwood, Stuart K.
中科院分区：
文献类型：
--
作者：
Marnbula, Salarnatu S.;Stevenson, Mary Ann;Calderwood, Stuart K.
热休克蛋白70 （Hsp70）从多种类型的细胞中释放，并在炎症和免疫反应中发挥重要的信号作用。然而，Hsp70不包含一致的分泌信号，因此不能通过常规机制穿过质膜。然而，Hsp70可以通过独立于新生Hsp70合成或细胞死亡的活性机制从细胞中释放出来。这种途径类似于无领导蛋白白细胞介素1 β所利用的途径。Hsp70释放通过内溶酶体隔室转运，并被溶酶体性化合物抑制。此外，Hsp70的分泌率与细胞表面溶酶体标记物LAMP1的出现密切相关，进一步提示了内溶酶体的作用。Hsp70进入这个分泌区似乎涉及abc家族转运蛋白。虽然通过溶酶体途径触发Hsp70释放的细胞信号在很大程度上是未知的，但最近的数据表明细胞外ATP具有调节作用。这些机制也与白细胞介素1分泌相同。释放后，Hsp70与邻近细胞结合，表明分泌蛋白参与与邻近细胞表面的旁分泌或自分泌相互作用。因此，对Hsp70的分泌机制有了初步的了解。需要进一步的研究来充分阐明Hsp70靶向非规范分泌途径及其调控的机制。(C) 2007爱思唯尔公司版权所有。
Heat shock protein 70 (Hsp70) is released from cells of many types and plays a significant signaling role, particularly in the inflammatory and immune responses. However, Hsp70 does not contain a consensus secretory signal and thus cannot traverse the plasma membrane by conventional mechanisms. However, Hsp70 can be released from cells by active mechanism that are independent of de novo Hsp70 synthesis or cell death. This pathway is similar to one utilized by the leaderless protein interleukin 1 beta. Hsp70 release involves transit through an endolysosomal compartment and is inhibited by lysosomotropic compounds. In addition, the rate of Hsp70 secretion correlates well with the appearance of the lysosomal marker LAMP1 on the cell surface, further suggesting the role for endolysosomes. The entry of Hsp70 into this secretory compartment appears to involve the ABC-family transporter proteins. While the cell signals involved in triggering Hsp70 release through this lysosomal pathway are largely unknown, recent data suggest a regulatory role for extracellular ATP. These mechanisms are also shared by interleukin 1 beta secretion. Following release it has been shown that Hsp70 binds to adjacent cells, suggesting that the secreted protein participates in paracrine or autocrine interactions with adjacent cell surfaces. Thus an outline is beginning to of the mechanisms of Hsp70 secretion. Much further study will be required to fully elucidate mechanisms involved in targeting Hsp70 towards the non-canonical secretion pathways and its regulation. (C) 2007 Elsevier Inc. All rights reserved.