Hsp90-mediated cytosolic refolding of exogenous proteins internalized by dendritic cells
Hsp90-mediated cytosolic refolding of exogenous proteins internalized by dendritic cells
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DOI：
10.1038/sj.emboj.7601941
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发表时间：
2008-01-09
期刊：
影响因子：
11.4
通讯作者：
Cresswell, Peter
中科院分区：
文献类型：
--
作者：
Giodini, Alessandra;Cresswell, Peter
树突状细胞通过液相摄取和受体介导的内吞作用有效地内化外源蛋白抗原。这些抗原通过转移到细胞质中进行蛋白酶体降解，从而促进交叉呈递，从而释放出免疫原性肽，这些肽在被转运到内质网（ER）后可以与主要组织相容性复合体（MHC） I类分子结合。然后在细胞表面表达MHC i类肽复合物并呈递给CD8(+) T细胞。在这里，我们表明内化的蛋白质可以有另一种命运。内化后，蛋白质首先展开，通过与内质网相关降解（ERAD）相关的途径转运到细胞质中。随后，未折叠的蛋白可以在伴侣蛋白Hsp90的帮助下进行细胞质重折叠。这些观察结果不仅阐明了内吞作用后调节胞质进入的细胞过程，而且还证明了功能蛋白可能在树突状细胞的胞质中重新获得活性。
Dendritic cells efficiently internalize exogenous protein antigens by fluid-phase uptake and receptor-mediated endocytosis. Such antigens contribute to cross-presentation by being translocated into the cytosol for proteasomal degradation, which liberates immunogenic peptides that can bind to major histocompatibility complex (MHC) class I molecules after being transported into the endoplasmic reticulum (ER). MHC class I-peptide complexes are then expressed on the cell surface and presented to CD8(+) T cells. Here we show that internalized proteins can have an alternative fate. After internalization, proteins are first unfolded to allow translocation into the cytosol using a pathway related to ER-associated degradation (ERAD). Subsequently the unfolded proteins can undergo cytosolic refolding assisted by the chaperone Hsp90. These observations not only clarify the cellular processes regulating cytosolic access following endocytosis, but also demonstrate that functional proteins can potentially regain their activity in the cytosol of dendritic cells.