Membrane protein targeting to the MVB/lysosome.

Membrane protein targeting to the MVB/lysosome.
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DOI:
10.1021/cr800473s
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发表时间:
2009-04
期刊:
影响因子:
62.1
通讯作者:
Katzmann, David J.
Katzmann, David J.
中科院分区:
化学1区
文献类型:
--
作者:
Davies, Brian A.;Lee, Jacqueline R. E.;Oestreich, Andrea J.;Katzmann, David J.

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细胞主要通过质膜内的受体、转运蛋白和通道的功能来感知和响应它们的环境。为了使细胞对环境信号做出适当的反应,它们必须在细胞表面保持适当的蛋白质补充。这涉及将蛋白质递送到细胞表面并在必要时将其去除。内吞途径内的多泡体(MVB)分选反应为终止溶酶体内降解的膜整合蛋白的功能提供了重要的细胞机制(综述见参考文献1-3)。MVB分选机器识别内吞货物的子集并将它们集中到内体膜内的区域中。然后这些切片以小泡的形式出芽进入内体的内腔,通过电子显微镜观察,使内体具有多泡的外观。随后MVB与溶酶体的融合将这些腔内囊泡递送至溶酶体的水解环境,在此囊泡的脂质和蛋白质内容物被降解(综述见参考文献4)。在MVB分选期间,膜内陷到内体腔中的拓扑结构(从胞质中脱出)类似于出芽过程,其中包膜病毒(包括HIV-1和埃博拉病毒)从细胞中排出(图1)。病毒结构蛋白,如来自HIV-1的Gag和来自埃博拉病毒的VP 40,利用MVB分选机制从质膜出芽或进入细胞内区室,随后从细胞中释放(参考文献5和6)。因此,MVB分选机制对于病毒复制和内吞蛋白的溶酶体递送都是重要的。此外,许多最近的研究已经显示了MVB分选机制在胞质分裂的后期步骤中的作用,7-13强调了这种机制对于相似膜拓扑结构的不同细胞过程的重要性。MVB分选在整个真核生物中是保守的,并且在酵母和哺乳动物系统中的研究已经鉴定了一系列介导该反应的反式作用因子(参见参考文献2、14和15)。转运所需的内体分选复合物(ESCRT)和相关蛋白构成了这种机制的大部分。货物识别通过与Vps 27/Hrs-Hse 1/STAM复合物以及与ESCRT-1(Vps 23/Tsg 101、Vps 28、Vps 37和Mvb 12)的相互作用介导。16-20 ESCRT-II(Vps 22、Vps 25、Vps 36)似乎在ESCRT-I的下游或平行发挥作用,并且还被认为基于Vps 36内的泛素结合结构域活性与货物相互作用。21-25 ESCRT-II还用于促进ESCRT-III亚基的募集和组装(Vps 20/CHMP 6,Snf 7/CHMP 4,Vps 2/CHMP 2,Vps 24/CHMP 3,Did 2/CHMP 1,
Cells sense and respond to their environment largely through the function of receptors, transporters, and channels within the plasma membrane. For cells to appropriately respond to environmental cues, they must maintain the proper protein complement at the cell surface. This involves both delivering proteins to the cell surface and removing them when necessary. The multivesicular body (MVB) sorting reaction within the endocytic pathway provides an important cellular mechanism for terminating the function of integral membrane proteins destined for degradation within the lysosome (reviewed in refs 1-3). The MVB sorting machinery recognizes a subset of endocytic cargoes and concentrates them into regions within the endosomal membrane. These sections then bud as small vesicles into the lumen of the endosome, giving the endosome a multivesicular appearance by electron microscopy. Subsequent fusion of the MVB with the lysosome delivers these intralumenal vesicles to the hydrolytic environment of the lysosome, where the lipid and protein contents of the vesicles are degraded (reviewed in ref 4). The topology of membrane invagination into the endosomal lumen (exvagination from the cytosol) during MVB sorting is similar to the budding process whereby enveloped viruses, including HIV-1 and Ebola virus, egress from the cell (Figure 1). Viral structural proteins, such as Gag from HIV-1 and VP40 from Ebola virus, utilize the MVB sorting machinery to bud either from the plasma membrane or into an intracellular compartment for subsequent release from the cell (reviewed in refs 5 and 6). Therefore, the MVB sorting machinery is important both for viral replication and for lysosomal delivery of endocytosed proteins. In addition, a number of recent studies have shown a role for the MVB sorting machinery in late steps of cytokinesis, 7-13 emphasizing the importance of this machinery for diverse cellular processes of similar membrane topology.MVB sorting is conserved throughout eukaryotes, and studies in both yeast and mammalian systems have identified a series of trans-acting factors that mediate this reaction (reviewed in refs 2, 14, and 15). The endosomal sorting complexes required for transport (ESCRTs) and associated proteins constitute the majority of this machinery. Cargo recognition is mediated by interactions with the Vps27/Hrs-Hse1/STAM complex as well as with ESCRT-I (Vps23/Tsg101, Vps28, Vps37, and Mvb12). 16-20 ESCRT-II (Vps22, Vps25, Vps36) appears to function downstream or in parallel to ESCRT-I and is also believed to interact with cargo based on ubiquitin-binding domain activity within Vps36. 21-25 ESCRT-II additionally serves to facilitate the recruitment and assembly of ESCRT-III subunits (Vps20/CHMP6, Snf7/CHMP4, Vps2/CHMP2, Vps24/CHMP3, Did2/CHMP1,
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影响因子: --
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