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Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes. ESCRT-III/Vps4膜重构和裂变复合物的结构、功能和动力学。
IF 11.3 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2018-10-06 Epub Date: 2018-08-10 DOI: 10.1146/annurev-cellbio-100616-060600
John McCullough, Adam Frost, Wesley I Sundquist

The endosomal sorting complexes required for transport (ESCRT) pathway mediates cellular membrane remodeling and fission reactions. The pathway comprises five core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble complexes are typically recruited to target membranes by site-specific adaptors that bind one or both of the early-acting ESCRT factors: ALIX and ESCRT-I/ESCRT-II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane-bound filaments that recruit the AAA ATPase Vps4. Together, ESCRT-III filaments and Vps4 remodel and sever membranes. Here, we review recent advances in our understanding of the structures, activities, and mechanisms of the ESCRT-III and Vps4 machinery, including the first high-resolution structures of ESCRT-III filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside-in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated membrane fission.

转运所需的内体分选复合物(ESCRT)途径介导细胞膜重塑和分裂反应。该途径包括五个核心复合物:ALIX、ESCRT-I、ESCRT-II、ESCRTIII和Vps4。这些可溶性复合物通常通过结合一种或两种早期作用的ESCRT因子(ALIX和ESCRT-I/ESTRT-II)的位点特异性衔接子募集到靶膜上。这些因子反过来将ESCRT-III亚基组装成膜结合丝,募集AAA ATPase Vps4。ESCRT-III细丝和Vps4一起重塑和切断膜。在这里,我们回顾了我们对ESCRT-III和Vps4机制的结构、活性和机制的理解的最新进展,包括ESCRT-IIII细丝的第一个高分辨率结构,组装的Vps4酶与ESCRT-III底物的复合物,发现ESCRT-III/Vps4复合物可以促进内外膜裂变反应,以及ESCRT介导的膜裂变的新兴机制模型。
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引用次数: 176
Assembly and Positioning of the Oocyte Meiotic Spindle. 卵母细胞减数分裂纺锤体的组装和定位。
IF 11.3 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2018-10-06 Epub Date: 2018-07-20 DOI: 10.1146/annurev-cellbio-100616-060553
Binyam Mogessie, Kathleen Scheffler, Melina Schuh

Fertilizable eggs develop from diploid precursor cells termed oocytes. Once every menstrual cycle, an oocyte matures into a fertilizable egg in the ovary. To this end, the oocyte eliminates half of its chromosomes into a small cell termed a polar body. The egg is then released into the Fallopian tube, where it can be fertilized. Upon fertilization, the egg completes the second meiotic division, and the mitotic division of the embryo starts. This review highlights recent work that has shed light on the cytoskeletal structures that drive the meiotic divisions of the oocyte in mammals. In particular, we focus on how mammalian oocytes assemble a microtubule spindle in the absence of centrosomes, how they position the spindle in preparation for polar body extrusion, and how the spindle segregates the chromosomes. We primarily focus on mouse oocytes as a model system but also highlight recent insights from human oocytes.

受精卵由称为卵母细胞的二倍体前体细胞发育而来。每一个月经周期,卵母细胞都会在卵巢中成熟为可受精的卵子。为此,卵母细胞将其一半的染色体去除,形成一个称为极体的小细胞。然后卵子被释放到输卵管中,在那里受精。受精后,卵子完成第二次减数分裂,胚胎开始有丝分裂。这篇综述强调了最近的工作,这些工作揭示了驱动哺乳动物卵母细胞减数分裂的细胞骨架结构。特别是,我们关注哺乳动物卵母细胞如何在没有中心体的情况下组装微管纺锤体,它们如何定位纺锤体为极体挤出做准备,以及纺锤体如何分离染色体。我们主要关注作为模型系统的小鼠卵母细胞,但也强调了人类卵母细胞的最新见解。
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引用次数: 7
Trafficking of Adhesion and Growth Factor Receptors and Their Effector Kinases. 粘附和生长因子受体及其效应激酶的迁移。
IF 11.3 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2018-10-06 Epub Date: 2018-08-15 DOI: 10.1146/annurev-cellbio-100617-062559
Christina Schoenherr, Margaret C Frame, Adam Byron

Cell adhesion to macromolecules in the microenvironment is essential for the development and maintenance of tissues, and its dysregulation can lead to a range of disease states, including inflammation, fibrosis, and cancer. The biomechanical and biochemical mechanisms that mediate cell adhesion rely on signaling by a range of effector proteins, including kinases and associated scaffolding proteins. The intracellular trafficking of these must be tightly controlled in space and time to enable effective cell adhesion and microenvironmental sensing and to integrate cell adhesion with, and compartmentalize it from, other cellular processes, such as gene transcription, protein degradation, and cell division. Delivery of adhesion receptors and signaling proteins from the plasma membrane to unanticipated subcellular locales is revealing novel biological functions. Here, we review the expected and unexpected trafficking, and sites of activity, of adhesion and growth factor receptors and intracellular kinase partners as we begin to appreciate the complexity and diversity of their spatial regulation.

细胞与微环境中大分子的粘附对组织的发育和维持至关重要,其失调可导致一系列疾病,包括炎症、纤维化和癌症。介导细胞粘附的生物力学和生物化学机制依赖于一系列效应蛋白(包括激酶和相关的支架蛋白)发出的信号。这些蛋白在细胞内的运输必须在空间和时间上得到严格控制,以实现有效的细胞粘附和微环境感知,并将细胞粘附与基因转录、蛋白质降解和细胞分裂等其他细胞过程结合起来,使之相互隔离。将粘附受体和信号蛋白从质膜输送到意想不到的亚细胞位置,揭示了新的生物学功能。在此,我们回顾了粘附受体、生长因子受体和细胞内激酶伙伴的预期和意料之外的转运以及活动场所,从而开始了解其空间调控的复杂性和多样性。
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引用次数: 0
Stellate Cells in Tissue Repair, Inflammation, and Cancer. 星形细胞在组织修复、炎症和癌症中的作用。
IF 11.3 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2018-10-06 Epub Date: 2018-07-20 DOI: 10.1146/annurev-cellbio-100617-062855
Mara H Sherman

Stellate cells are resident lipid-storing cells of the pancreas and liver that transdifferentiate to a myofibroblastic state in the context of tissue injury. Beyond having roles in tissue homeostasis, stellate cells are increasingly implicated in pathological fibrogenic and inflammatory programs that contribute to tissue fibrosis and that constitute a growth-permissive tumor microenvironment. Although the capacity of stellate cells for extracellular matrix production and remodeling has long been appreciated, recent research efforts have demonstrated diverse roles for stellate cells in regulation of epithelial cell fate, immune modulation, and tissue health. Our present understanding of stellate cell biology in health and disease is discussed here, as are emerging means to target these multifaceted cells for therapeutic benefit.

星状细胞是胰腺和肝脏的常驻脂质储存细胞,在组织损伤的情况下可转分化为肌成纤维细胞状态。除了在组织稳态中发挥作用外,星状细胞越来越多地参与病理纤维化和炎症程序,这些程序有助于组织纤维化,并构成允许生长的肿瘤微环境。尽管星状细胞产生细胞外基质和重塑的能力长期以来一直受到重视,但最近的研究表明,星状细胞在调节上皮细胞命运、免疫调节和组织健康方面具有多种作用。我们目前对星状细胞生物学在健康和疾病方面的理解在这里讨论,以及针对这些多面细胞的治疗益处的新方法。
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引用次数: 63
Caveolae: Structure, Function, and Relationship to Disease. 小窝:结构、功能及其与疾病的关系。
IF 11.3 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2018-10-06 DOI: 10.1146/annurev-cellbio-100617-062737
Robert G Parton

The plasma membrane of eukaryotic cells is not a simple sheet of lipids and proteins but is differentiated into subdomains with crucial functions. Caveolae, small pits in the plasma membrane, are the most abundant surface subdomains of many mammalian cells. The cellular functions of caveolae have long remained obscure, but a new molecular understanding of caveola formation has led to insights into their workings. Caveolae are formed by the coordinated action of a number of lipid-interacting proteins to produce a microdomain with a specific structure and lipid composition. Caveolae can bud from the plasma membrane to form an endocytic vesicle or can flatten into the membrane to help cells withstand mechanical stress. The role of caveolae as mechanoprotective and signal transduction elements is reviewed in the context of disease conditions associated with caveola dysfunction.

真核细胞的质膜不是简单的脂质和蛋白质片,而是分化成具有重要功能的亚结构域。在许多哺乳动物细胞中,小泡是最丰富的表面亚域。小窝的细胞功能长期以来一直不为人所知,但对小窝形成的新的分子理解使人们对其工作原理有了深入的了解。微泡是由许多脂质相互作用蛋白协同作用形成的,产生具有特定结构和脂质组成的微结构域。小泡可以从质膜上发芽形成内吞囊泡,也可以平展到膜上,帮助细胞承受机械应力。在与小窝功能障碍相关的疾病条件下,回顾了小窝作为机械保护和信号转导元件的作用。
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引用次数: 165
Mucins and Their Role in Shaping the Functions of Mucus Barriers. 粘蛋白及其在塑造粘液屏障功能方面的作用。
IF 11.3 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2018-10-06 Epub Date: 2018-05-11 DOI: 10.1146/annurev-cellbio-100617-062818
C E Wagner, K M Wheeler, K Ribbeck

We review what is currently understood about how the structure of the primary solid component of mucus, the glycoprotein mucin, gives rise to the mechanical and biochemical properties of mucus that are required for it to perform its diverse physiological roles. Macroscale processes such as lubrication require mucus of a certain stiffness and spinnability, which are set by structural features of the mucin network, including the identity and density of cross-links and the degree of glycosylation. At the microscale, these same features affect the mechanical environment experienced by small particles and play a crucial role in establishing an interaction-based filter. Finally, mucin glycans are critical for regulating microbial interactions, serving as receptor binding sites for adhesion, as nutrient sources, and as environmental signals. We conclude by discussing how these structural principles can be used in the design of synthetic mucin-mimetic materials and provide suggestions for directions of future work in this field.

我们回顾了目前对粘液的主要固体成分--糖蛋白粘蛋白的结构如何产生粘液的机械和生化特性的理解,而粘液的机械和生化特性正是粘液发挥各种生理作用所必需的。润滑等宏观过程要求粘液具有一定的硬度和可纺性,这是由粘蛋白网络的结构特征决定的,包括交联的特性和密度以及糖基化程度。在微观尺度上,这些特征同样会影响小颗粒所经历的机械环境,并在建立基于相互作用的过滤器方面发挥关键作用。最后,粘蛋白聚糖是调节微生物相互作用的关键,可作为粘附的受体结合位点、营养源和环境信号。最后,我们讨论了如何将这些结构原理用于设计合成粘蛋白仿生材料,并对这一领域未来的工作方向提出了建议。
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引用次数: 0
Regulation of Neuronal Differentiation, Function, and Plasticity by Alternative Splicing. 选择性剪接对神经元分化、功能和可塑性的调节。
IF 11.3 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2018-10-06 Epub Date: 2018-07-20 DOI: 10.1146/annurev-cellbio-100617-062826
Elisabetta Furlanis, Peter Scheiffele

Posttranscriptional mechanisms provide powerful means to expand the coding power of genomes. In nervous systems, alternative splicing has emerged as a fundamental mechanism not only for the diversification of protein isoforms but also for the spatiotemporal control of transcripts. Thus, alternative splicing programs play instructive roles in the development of neuronal cell type-specific properties, neuronal growth, self-recognition, synapse specification, and neuronal network function. Here we discuss the most recent genome-wide efforts on mapping RNA codes and RNA-binding proteins for neuronal alternative splicing regulation. We illustrate how alternative splicing shapes key steps of neuronal development, neuronal maturation, and synaptic properties. Finally, we highlight efforts to dissect the spatiotemporal dynamics of alternative splicing and their potential contribution to neuronal plasticity and the mature nervous system.

转录后机制为扩展基因组的编码能力提供了强有力的手段。在神经系统中,选择性剪接不仅是蛋白质异构体多样化的基本机制,也是转录物时空控制的基本机制。因此,可选择的剪接程序在神经元细胞类型特异性、神经元生长、自我识别、突触规范和神经网络功能的发展中起着指导性作用。在这里,我们讨论了最近在绘制RNA编码和RNA结合蛋白以调控神经元选择性剪接方面的全基因组研究成果。我们说明如何选择剪接形状神经元发育,神经元成熟和突触特性的关键步骤。最后,我们重点分析了选择性剪接的时空动态及其对神经元可塑性和成熟神经系统的潜在贡献。
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引用次数: 95
Axon Regeneration in the Central Nervous System: Facing the Challenges from the Inside. 中枢神经系统轴突再生:面对来自内部的挑战。
IF 11.3 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2018-10-06 Epub Date: 2018-07-25 DOI: 10.1146/annurev-cellbio-100617-062508
Michele Curcio, Frank Bradke

After an injury in the adult mammalian central nervous system (CNS), lesioned axons fail to regenerate. This failure to regenerate contrasts with axons' remarkable potential to grow during embryonic development and after an injury in the peripheral nervous system (PNS). Several intracellular mechanisms-including cytoskeletal dynamics, axonal transport and trafficking, signaling and transcription of regenerative programs, and epigenetic modifications-control axon regeneration. In this review, we describe how manipulation of intrinsic mechanisms elicits a regenerative response in different organisms and how strategies are implemented to form the basis of a future regenerative treatment after CNS injury.

成年哺乳动物中枢神经系统(CNS)损伤后,受损的轴突不能再生。这种再生的失败与轴突在胚胎发育和周围神经系统(PNS)损伤后的显著生长潜力形成对比。一些细胞内机制,包括细胞骨架动力学,轴突运输和运输,再生程序的信号和转录,以及表观遗传修饰,控制轴突再生。在这篇综述中,我们描述了如何操纵内在机制在不同的生物体中引发再生反应,以及如何实施策略以形成未来中枢神经系统损伤后再生治疗的基础。
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引用次数: 120
Principles of Ubiquitin-Dependent Signaling. 泛素依赖性信号传导原理
IF 11.3 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2018-10-06 Epub Date: 2018-08-15 DOI: 10.1146/annurev-cellbio-100617-062802
Eugene Oh, David Akopian, Michael Rape

Ubiquitylation is an essential posttranslational modification that controls cell division, differentiation, and survival in all eukaryotes. By combining multiple E3 ligases (writers), ubiquitin-binding effectors (readers), and de-ubiquitylases (erasers) with functionally distinct ubiquitylation tags, the ubiquitin system constitutes a powerful signaling network that is employed in similar ways from yeast to humans. Here, we discuss conserved principles of ubiquitin-dependent signaling that illustrate how this posttranslational modification shapes intracellular signaling networks to establish robust development and homeostasis throughout the eukaryotic kingdom.

泛素化是一种重要的翻译后修饰,控制着所有真核生物的细胞分裂、分化和存活。通过将多种E3连接酶(写入器)、泛素结合效应物(读取器)和去泛素化酶(擦除器)与功能不同的泛素化标签相结合,泛素系统构成了一个强大的信号网络,从酵母到人类都以类似的方式使用。在这里,我们讨论了泛素依赖信号传导的保守原理,说明了这种翻译后修饰如何塑造细胞内信号网络,从而在整个真核生物王国中建立健全的发育和稳态。
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引用次数: 197
Sortase A: A Model for Transpeptidation and Its Biological Applications. 分类酶A:转肽酶模型及其生物学应用。
IF 11.3 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2018-10-06 Epub Date: 2018-08-15 DOI: 10.1146/annurev-cellbio-100617-062527
Novalia Pishesha, Jessica R Ingram, Hidde L Ploegh

Molecular biologists and chemists alike have long sought to modify proteins with substituents that cannot be installed by standard or even advanced genetic approaches. We here describe the use of transpeptidases to achieve these goals. Living systems encode a variety of transpeptidases and peptide ligases that allow for the enzyme-catalyzed formation of peptide bonds, and protein engineers have used directed evolution to enhance these enzymes for biological applications. We focus primarily on the transpeptidase sortase A, which has become popular over the past few years for its ability to perform a remarkably wide variety of protein modifications, both in vitro and in living cells.

长期以来,分子生物学家和化学家都在寻求用标准甚至先进的遗传方法无法安装的取代基来修饰蛋白质。我们在这里描述转肽酶的使用来实现这些目标。生命系统编码多种转肽酶和肽连接酶,这些转肽酶和肽连接酶允许酶催化形成肽键,蛋白质工程师已经使用定向进化来增强这些酶的生物学应用。我们主要关注转肽酶分选酶A,它在过去几年中因其在体外和活细胞中进行非常广泛的蛋白质修饰的能力而变得流行。
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引用次数: 75
期刊
Annual review of cell and developmental biology
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