Endoplasmic Reticulum-Endosome Contact Sites: Specialized Interfaces for Orchestrating Endosomal Tubule Fission?
Endoplasmic Reticulum-Endosome Contact Sites: Specialized Interfaces for Orchestrating Endosomal Tubule Fission?
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DOI：
10.1021/acs.biochem.8b01176
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发表时间：
2018-12-11
期刊：
影响因子：
2.9
通讯作者：
Cullen, Peter J.
中科院分区：
文献类型：
--
作者：
Daly, James L.;Cullen, Peter J.
内膜系统使得能够将单独的生物过程委托给真核细胞内空间上不同的细胞器。虽然维持这些隔室的独特生化组成是必要的，但细胞器间的通讯提供了一种动态交换蛋白质、脂质和离子的手段，使真核细胞能够达到一定的复杂程度，取代其各部分的总和。最近，膜接触位点（MCSs）已成为一种新的机制，细胞器之间的串扰，除了典型的过程囊泡膜贩运。最值得注意的是，内质网（ER）的小管已被证明接触质膜，线粒体和内体，以及其他细胞器。ER MCSs将相对的细胞器膜束缚在30 nm内而不发生膜融合。ER MCSs的一系列功能迄今已被确立，包括双向脂质转移，Ca 2+交换，以及对细胞器运输和定位的微调控制。一个迷人的新兴概念是管状ER预测在细胞器裂变的调节中的潜在作用。在最近发表在《细胞》杂志上的一篇文章中，Hoyer等人研究了ER−内体MCS在内体分裂的调控和时机中的作用，方法是利用生物素连接酶BioID开发一种邻近依赖性标记策略，以鉴定动态内体小管附近的新型ER蛋白。1内体再循环是一个必不可少的过程，其中跨膜蛋白（称为“货物”）被其胞质序列基序识别，并随着内体成熟并与溶酶体融合而从降解命运中分选出来。这种识别是通过一系列进化上保守的蛋白质复合物来实现的，如逆转录聚合物或回收复合物，它们整合到更高级的外壳结构中。2这些多蛋白组装体将货物聚集到内体膜上的检索子域中，并介导管状结构的生物发生，这些管状结构最终分离并运输到受体隔室，如质膜或trans-Golgi网络（TGN）。尽管这种基于序列的货物识别和小管形成的分子细节变得更加清晰，但小管断裂的最后阶段仍然不明确。ER-内体接触位点被认为通过在内体芽上施加紧密的扩散屏障和确定小管分裂的位点来影响内体分选和运输的过程。1 WASH复合物是核内体上分支肌动蛋白成核Arp 2/3复合物的主要激活剂，定位于出芽检索亚结构域，并在沿小管沿着聚集再循环复合物中起协调作用。2通过将BioID标记到WASH复合体亚基FAM 21上，Hoyer等人建立了一个将邻近蛋白生物素化到该瞬时亚结构域的系统。标记蛋白质的质谱分析显示，除了先前建立的ER MCS蛋白质VAPA/B之外，ER跨膜蛋白质TMCC 1是FAM 21的近端蛋白质。当表达为GFP融合蛋白时，TMCC 1（及其旁系同源物TMCC 2和TMCC 3）定位于外周ER中的离散结构域，其在分裂前与Rab 7阳性出芽的内体小管共定位。这代表了ER-内体MCS的其他标志物的独特分布，例如主要接触内体液泡部分的Protrudin，表明MCS形成的特定位置由有助于其功能的精确蛋白质-蛋白质相互作用控制。而且...
The endomembrane system enables the delegation of separate biological processes to spatially distinct organelles within eukaryotic cells. While it is imperative that the unique biochemical compositions of these compartments are maintained, interorganellar communication provides a means to dynamically exchange proteins, lipids, and ions, allowing eukaryotic cells to achieve a level of complexity that supersedes the sum of its parts. Recently, membrane contact sites (MCSs) have emerged as a novel mechanism for crosstalk between organelles, in addition to canonical processes of vesicular membrane trafficking. Most notably, tubules of the endoplasmic reticulum (ER) have been demonstrated to contact the plasma membrane, mitochondria, and endosomes, among other organelles. ER MCSs tether the opposing organelle membrane within 30 nm without the occurrence of membrane fusion. A range of functions of ER MCSs have thus far been established, including bidirectional lipid transfer, Ca2+ exchange, and fine-tuned control over organelle transport and positioning. A fascinating emerging concept is the potential role for tubular ER projections in the regulation of organelle fission. In a recent publication in Cell, Hoyer et al. investigated the role of ER− endosome MCSs in the regulation and timing of endosomal fission by developing a proximitydependent labeling strategy with the biotin ligase enzyme BioID to identify novel ER proteins within the vicinity of dynamic endosomal tubules. 1 Endosomal recycling is an essential process whereby transmembrane proteins (termed “cargoes”) are recognized by their cytosolic sequence motifs and sorted away from a degradative fate as endosomes mature and fuse with lysosomes. This recognition is achieved by an array of evolutionarily conserved protein complexes, such as the retromer or retriever complexes, that integrate into higher-order coat structures. 2 These multiprotein assemblies corral cargo into a retrieval subdomain on the endosomal membrane and mediate the biogenesis of tubular structures that ultimately separate and traffic to an acceptor compartment such as the plasma membrane or trans-Golgi network (TGN). Despite the molecular details of this sequence-based cargo recognition and tubule formation becoming clearer, the final stages of tubule scission remain ambiguous. ER− endosome contact sites have been suggested to influence the process of endosomal sorting and trafficking by imposing a tight diffusion barrier on endosomal buds and defining the sites of tubule fission. 1 The WASH complex, which is the major activator of the branched actin-nucleating Arp2/3 complex on endosomes, localizes to budding retrieval subdomains and plays an orchestrating role in the clustering of recycling complexes along the tubule. 2 By tagging BioID to the WASH complex subunit FAM21, Hoyer et al. establish a system for biotinylating vicinal proteins to this transient subdomain. Mass spectrometric analysis of labeled proteins revealed the ER transmembrane protein TMCC1 as a proximal protein to FAM21, in addition to a previously established ER MCS protein, VAPA/B. When expressed as a GFP fusion protein, TMCC1 (and its paralogues, TMCC2 and TMCC3) localized to discrete domains in the peripheral ER that colocalize with Rab7-positive budding endosomal tubules prior to fission. This represents a distinct distribution to other markers of ER− endosome MCSs, such as Protrudin that primarily contacts the vacuolar portion of the endosome, suggesting that the specific location of MCS formation is governed by precise protein− protein interactions that contribute to its function. Moreover …