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Current Biology : CB Jan 2016Approximately one third of a cell's proteins are destined to function outside the cell's boundaries or while embedded within cellular membranes. Ensuring these proteins... (Review)
Review
Approximately one third of a cell's proteins are destined to function outside the cell's boundaries or while embedded within cellular membranes. Ensuring these proteins reach their diverse final destinations with temporal and spatial accuracy is essential for cellular physiology. In eukaryotes, a set of interconnected organelles form the secretory pathway, which encompasses the terrain that these proteins must navigate on their journey from their site of synthesis on the ribosome to their final destinations. Traffic of proteins within the secretory pathway is directed by cargo-bearing vesicles that transport proteins from one compartment to another. Key steps in vesicle-mediated trafficking include recruitment of specific cargo proteins, which must collect locally where a vesicle forms, and release of an appropriate cargo-containing vessel from the donor organelle (Figure 1). The newly formed vesicle can passively diffuse across the cytoplasm, or can catch a ride on the cytoskeleton to travel directionally. Once the vesicle arrives at its precise destination, the membrane of the carrier merges with the destination membrane to deliver its cargo.
Topics: Animals; COP-Coated Vesicles; Cytoplasm; Humans; Organelles; Protein Transport; Saccharomyces cerevisiae Proteins; Vesicular Transport Proteins
PubMed: 26811885
DOI: 10.1016/j.cub.2015.12.017 -
Current Opinion in Structural Biology Aug 2022Clathrin-mediated endocytosis enables selective uptake of molecules into cells in response to changing cellular needs. It occurs through assembly of coat components... (Review)
Review
Clathrin-mediated endocytosis enables selective uptake of molecules into cells in response to changing cellular needs. It occurs through assembly of coat components around the plasma membrane that determine vesicle contents and facilitate membrane bending to form a clathrin-coated transport vesicle. In this review we discuss recent cryo-electron microscopy structures that have captured a series of events in the life cycle of a clathrin-coated vesicle. Both single particle analysis and tomography approaches have revealed details of the clathrin lattice structure itself, how AP2 may interface with clathrin within a coated vesicle and the importance of PIP2 binding for assembly of the yeast adaptors Sla2 and Ent1 on the membrane. Within cells, cryo-electron tomography of clathrin in flat lattices and high-speed AFM studies provided new insights into how clathrin morphology can adapt during CCV formation. Thus, key mechanical processes driving clathrin-mediated endocytosis have been captured through multiple techniques working in partnership.
Topics: Cell Membrane; Clathrin; Clathrin-Coated Vesicles; Coated Vesicles; Cryoelectron Microscopy; Endocytosis; Saccharomyces cerevisiae
PubMed: 35872561
DOI: 10.1016/j.sbi.2022.102427 -
FEBS Letters Mar 2023COPI-coated vesicles mediate transport between Golgi stacks and retrograde transport from the Golgi to the endoplasmic reticulum. The COPI coat exists as a stable... (Review)
Review
COPI-coated vesicles mediate transport between Golgi stacks and retrograde transport from the Golgi to the endoplasmic reticulum. The COPI coat exists as a stable heptameric complex in the cytosol termed coatomer and is recruited en bloc to the membrane for vesicle formation. Recruitment of COPI onto membranes is mediated by the Arf family of small GTPases, which, in their GTP-bound state, bind both membrane and coatomer. Arf GTPases also influence cargo selection, vesicle scission and vesicle uncoating. Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) regulate nucleotide binding by Arf GTPases. To understand the mechanism of COPI-coated vesicle trafficking, it is necessary to characterize the interplay between coatomer and Arf GTPases and their effectors. It is also necessary to understand interactions between coatomer and cargo, cargo adaptors/receptors and tethers facilitating binding to the target membrane. Here, we summarize current knowledge of COPI coat protein structure; we describe how structural and biochemical studies contributed to this knowledge; we review mechanistic insights into COPI vesicle biogenesis and disassembly; and we discuss the potential to answer open questions in the field.
Topics: Humans; ADP-Ribosylation Factors; Carrier Proteins; COP-Coated Vesicles; Enzyme Activation; GTPase-Activating Proteins; Guanine Nucleotide Exchange Factors; Substrate Specificity
PubMed: 36513395
DOI: 10.1002/1873-3468.14560 -
Traffic (Copenhagen, Denmark) Dec 2015The purification of coated vesicles and the discovery of clathrin by Barbara Pearse in 1975 was a landmark in cell biology. Over the past 40 years, work from many labs... (Review)
Review
The purification of coated vesicles and the discovery of clathrin by Barbara Pearse in 1975 was a landmark in cell biology. Over the past 40 years, work from many labs has uncovered the molecular details of clathrin and its associated proteins, including how they assemble into a coated vesicle and how they select cargo. Unexpected connections have been found with signalling, development, neuronal transmission, infection, immunity and genetic disorders. But there are still a number of unanswered questions, including how clathrin-mediated trafficking is regulated and how the machinery evolved.
Topics: Animals; Cell Biology; Clathrin; Clathrin-Coated Vesicles; Coated Pits, Cell-Membrane; History, 20th Century; History, 21st Century; Humans; Models, Molecular; Protein Conformation; Protein Transport
PubMed: 26403691
DOI: 10.1111/tra.12335 -
Cold Spring Harbor Perspectives in... Sep 2012Neurons can sustain high rates of synaptic transmission without exhausting their supply of synaptic vesicles. This property relies on a highly efficient local endocytic... (Review)
Review
Neurons can sustain high rates of synaptic transmission without exhausting their supply of synaptic vesicles. This property relies on a highly efficient local endocytic recycling of synaptic vesicle membranes, which can be reused for hundreds, possibly thousands, of exo-endocytic cycles. Morphological, physiological, molecular, and genetic studies over the last four decades have provided insight into the membrane traffic reactions that govern this recycling and its regulation. These studies have shown that synaptic vesicle endocytosis capitalizes on fundamental and general endocytic mechanisms but also involves neuron-specific adaptations of such mechanisms. Thus, investigations of these processes have advanced not only the field of synaptic transmission but also, more generally, the field of endocytosis. This article summarizes current information on synaptic vesicle endocytosis with an emphasis on the underlying molecular mechanisms and with a special focus on clathrin-mediated endocytosis, the predominant pathway of synaptic vesicle protein internalization.
Topics: Actin Cytoskeleton; Clathrin; Clathrin-Coated Vesicles; Endocytosis; Exocytosis; Intracellular Membranes; Membrane Fusion; Models, Biological; Phosphatidylinositols; Protein Transport; Synaptic Transmission; Synaptic Vesicles
PubMed: 22763746
DOI: 10.1101/cshperspect.a005645 -
Cold Spring Harbor Perspectives in... Nov 2011The Golgi serves as a hub for intracellular membrane traffic in the eukaryotic cell. Transport within the early secretory pathway, that is within the Golgi and from the... (Review)
Review
The Golgi serves as a hub for intracellular membrane traffic in the eukaryotic cell. Transport within the early secretory pathway, that is within the Golgi and from the Golgi to the endoplasmic reticulum, is mediated by COPI-coated vesicles. The COPI coat shares structural features with the clathrin coat, but differs in the mechanisms of cargo sorting and vesicle formation. The small GTPase Arf1 initiates coating on activation and recruits en bloc the stable heptameric protein complex coatomer that resembles the inner and the outer shells of clathrin-coated vesicles. Different binding sites exist in coatomer for membrane machinery and for the sorting of various classes of cargo proteins. During the budding of a COPI vesicle, lipids are sorted to give a liquid-disordered phase composition. For the release of a COPI-coated vesicle, coatomer and Arf cooperate to mediate membrane separation.
Topics: Binding Sites; Biological Transport; COP-Coated Vesicles; Endocytosis; Golgi Apparatus; Membrane Lipids; Mitosis; Models, Biological; Protein Sorting Signals; Protein Transport; Secretory Pathway
PubMed: 21844168
DOI: 10.1101/cshperspect.a005231 -
FEBS Letters Sep 2022Endocytic trafficking underlies processes essential for plant growth and development, including the perception of and response to abiotic and extracellular stimuli,... (Review)
Review
Endocytic trafficking underlies processes essential for plant growth and development, including the perception of and response to abiotic and extracellular stimuli, post-Golgi and exocytic trafficking, and cytokinesis. Protein adaptors and regulatory factors of clathrin-mediated endocytosis that contribute to the formation of endocytic clathrin-coated vesicles are evolutionarily conserved. Yet, work of the last ten years has identified differences between the endocytic mechanisms of plants and Opisthokonts involving the endocytic adaptor TPLATE complex, the requirement of actin during CME, and the function of clathrin-independent endocytosis in the uptake of plant-specific plasma membrane proteins. Here, we review clathrin-mediated and -independent pathways in plants and describe recent advances enabled by new proteomic and imaging methods, and conditional perturbation of endocytosis. In addition, we summarize the formation and trafficking of clathrin-coated vesicles based on temporal and structural data garnered from high-resolution quantitative imaging studies. Finally, new information about the cross-talk between endocytosis and other endomembrane trafficking pathways and organelles will also be discussed.
Topics: Clathrin; Clathrin-Coated Vesicles; Cytokinesis; Endocytosis; Proteomics
PubMed: 35674447
DOI: 10.1002/1873-3468.14420 -
Seminars in Cell & Developmental Biology Feb 2011Vesicle trafficking is a highly regulated process that transports proteins and other cargoes through eukaryotic cells while maintaining cellular organization and... (Review)
Review
Vesicle trafficking is a highly regulated process that transports proteins and other cargoes through eukaryotic cells while maintaining cellular organization and compartmental identity. In order for cargo to reach the correct destination, each step of trafficking must impart specificity. During vesicle formation, this is achieved by coat proteins, which selectively incorporate cargo into the nascent vesicle. Classically, vesicle coats are thought to dissociate shortly after budding. However, recent studies suggest that coat proteins can remain on the vesicle en route to their destination, imparting targeting specificity by physically and functionally interacting with Rab-regulated tethering systems. This review focuses on how interactions among Rab GTPases, tethering factors, SNARE proteins, and vesicle coats contribute to vesicle targeting, fusion, and coat dynamics.
Topics: Animals; Biological Transport; Coated Vesicles; Humans; Protein Binding; Protein Subunits; rab GTP-Binding Proteins
PubMed: 20643221
DOI: 10.1016/j.semcdb.2010.07.003 -
Biochimica Et Biophysica Acta Aug 2012In eukaryotic cells, the endoplasmic reticulum (ER) is a major site of synthesis of both lipids and proteins, many of which must be transported to other organelles. The... (Review)
Review
In eukaryotic cells, the endoplasmic reticulum (ER) is a major site of synthesis of both lipids and proteins, many of which must be transported to other organelles. The COPII coat-comprising Sar1, Sec23/24, Sec13/31-generates transport vesicles that mediate the bulk of protein/lipid export from the ER. The coat exhibits remarkable flexibility in its ability to specifically select and accommodate a large number of cargoes with diverse properties. In this review, we discuss the fundamentals of COPII vesicle production and describe recent advances that further our understanding of just how flexible COPII cargo recruitment and vesicle formation may be. Large or bulky cargo molecules (e.g. collagen rods and lipoprotein particles) exceed the canonical size for COPII vesicles and seem to rely on the additional action of recently identified accessory molecules. Although the bulk of the research has focused on the fate of protein cargo, the mechanisms and regulation of lipid transport are equally critical to cellular survival. From their site of synthesis in the ER, phospholipids, sphingolipids and sterols exit the ER, either accompanying cargo in vesicles or directly across the cytoplasm shielded by lipid-transfer proteins. Finally, we highlight the current challenges to the field in addressing the physiological regulation of COPII vesicle production and the molecular details of how diverse cargoes, both proteins and lipids, are accommodated. This article is part of a Special Issue entitled Lipids and Vesicular Transport.
Topics: Animals; Biological Transport; COP-Coated Vesicles; Collagen; Endoplasmic Reticulum; GPI-Linked Proteins; Golgi Apparatus; Humans; Lipid Metabolism; Protein Isoforms; Vesicular Transport Proteins
PubMed: 22265716
DOI: 10.1016/j.bbalip.2012.01.005 -
Current Opinion in Cell Biology Aug 2012Eukaryotic cells face a logistical challenge in ensuring prompt and precise delivery of vesicular cargo to specific organelles within the cell. Coat protein complexes... (Review)
Review
Eukaryotic cells face a logistical challenge in ensuring prompt and precise delivery of vesicular cargo to specific organelles within the cell. Coat protein complexes select cargo and initiate vesicle formation, while multisubunit tethering complexes participate in the delivery of vesicles to target membranes. Understanding these macromolecular assemblies has greatly benefited from their structural characterization. Recent structural data highlight principles in coat recruitment and uncoating in both the endocytic and retrograde pathways, and studies on the architecture of tethering complexes provide a framework for how they might link vesicles to the respective acceptor compartments and the fusion machinery.
Topics: Adaptor Proteins, Vesicular Transport; Auxilins; Biological Transport; COP-Coated Vesicles; Coated Vesicles; Humans; Protein Subunits
PubMed: 22728063
DOI: 10.1016/j.ceb.2012.05.013