Review

Authors: Jie Li, Erpan Ahat, Yanzhuang Wang...

The Golgi apparatus is a central intracellular membrane-bound organelle with key functions in trafficking, processing, and sorting of newly synthesized membrane and secretory proteins and lipids. To best perform these functions, Golgi membranes form a unique stacked structure. The Golgi structure is dynamic but tightly regulated; it undergoes rapid disassembly and reassembly during the cell cycle of mammalian cells and is disrupted under certain stress and pathological conditions. In the past decade, significant amount of effort has been made to reveal the molecular mechanisms that regulate the Golgi membrane architecture and function. Here we review the major discoveries in the mechanisms of Golgi structure formation, regulation, and alteration in relation to its functions in physiological and pathological conditions to further our understanding of Golgi structure and function in health and diseases.

Topics: Animals; Biological Transport; Cell Cycle; Disease; Golgi Apparatus; Health; Humans; Intracellular Membranes; Stress, Physiological

PubMed: 31435807
DOI: 10.1007/978-3-030-23173-6_19

Authors: J F Presley, C Smith, K Hirschberg...

Topics: Animals; Biological Transport; Brefeldin A; COS Cells; Endoplasmic Reticulum; Golgi Apparatus; Green Fluorescent Proteins; Intracellular Membranes; Light; Luminescent Proteins; Membrane Glycoproteins; Microscopy, Video; Vesicular stomatitis Indiana virus; Video Recording; Viral Envelope Proteins

PubMed: 9658158
DOI: 10.1091/mbc.9.7.1617

Authors: Eric M Sawyer, Liv E Jensen, Janet B Meehl...

Rough endoplasmic reticulum (ER) sheets are a fundamental domain of the ER and the gateway into the secretory pathway. Although reticulon proteins stabilize high-curvature ER tubules, it is unclear whether other proteins scaffold the flat membranes of rough ER sheets. Through a proteomics screen using ER sheet-localized RNA-binding proteins as bait, we identify the sigma-1 receptor (SigmaR1) as an ER sheet-shaping factor. High-resolution live cell imaging and electron tomography assign SigmaR1 as an ER sheet-localized factor whose levels determine the amount of rough ER sheets in cells. Structure-guided mutagenesis and in vitro reconstitution on giant unilamellar vesicles further support a mechanism whereby SigmaR1 oligomers use their extended arrays of amphipathic helices to bind and flatten the lumenal leaflet of ER membranes to oppose membrane curvature and stabilize rough ER sheets.

Topics: Endoplasmic Reticulum; Receptors, sigma; Sigma-1 Receptor; Animals; Intracellular Membranes; Humans; RNA-Binding Proteins

PubMed: 38971154
DOI: 10.1016/j.devcel.2024.06.005

Authors: Georg Wolff, Ronald W A L Limpens, Jessika C Zevenhoven-Dobbe...

Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and messenger RNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. In this study, we used cellular cryo-electron microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a key role in coronavirus replication and thus constitutes a potential drug target.

Topics: Animals; Cryoelectron Microscopy; Cytoplasmic Vesicles; Electron Microscope Tomography; Intracellular Membranes; Mice; Murine hepatitis virus; RNA, Viral; Viral Nonstructural Proteins; Virus Replication

PubMed: 32763915
DOI: 10.1126/science.abd3629

Review

Authors: G K Voeltz, E M Sawyer, G Hajnóczky...

The view of organelles and how they operate together has changed dramatically over the last two decades. The textbook view of organelles was that they operated largely independently and were connected by vesicular trafficking and the diffusion of signals through the cytoplasm. We now know that all organelles make functional close contacts with one another, often called membrane contact sites. The study of these sites has moved to center stage in cell biology as it has become clear that they play critical roles in healthy and developing cells and during cell stress and disease states. Contact sites have important roles in intracellular signaling, lipid metabolism, motor-protein-mediated membrane dynamics, organelle division, and organelle biogenesis. Here, we summarize the major conceptual changes that have occurred in cell biology as we have come to appreciate how contact sites integrate the activities of organelles.

Topics: Biology; Cell Membrane; Mitochondrial Membranes; Organelles; Intracellular Membranes

PubMed: 38242082
DOI: 10.1016/j.cell.2023.11.040

Authors: Yixin Huang, Tongyun Wang, Lijie Zhong...

Coronaviruses remodel the intracellular host membranes during replication, forming double-membrane vesicles (DMVs) to accommodate viral RNA synthesis and modifications. SARS-CoV-2 non-structural protein 3 (nsp3) and nsp4 are the minimal viral components required to induce DMV formation and to form a double-membrane-spanning pore, essential for the transport of newly synthesized viral RNAs. The mechanism of DMV pore complex formation remains unknown. Here we describe the molecular architecture of the SARS-CoV-2 nsp3-nsp4 pore complex, as resolved by cryogenic electron tomography and subtomogram averaging in isolated DMVs. The structures uncover an unexpected stoichiometry and topology of the nsp3-nsp4 pore complex comprising 12 copies each of nsp3 and nsp4, organized in 4 concentric stacking hexamer rings, mimicking a miniature nuclear pore complex. The transmembrane domains are interdigitated to create a high local curvature at the double-membrane junction, coupling double-membrane reorganization with pore formation. The ectodomains form extensive contacts in a pseudo-12-fold symmetry, belting the pore complex from the intermembrane space. A central positively charged ring of arginine residues coordinates the putative RNA translocation, essential for virus replication. Our work establishes a framework for understanding DMV pore formation and RNA translocation, providing a structural basis for the development of new antiviral strategies to combat coronavirus infection.

Topics: Humans; Arginine; Cryoelectron Microscopy; Electron Microscope Tomography; Intracellular Membranes; Models, Molecular; Porosity; Protein Domains; RNA Transport; RNA, Viral; SARS-CoV-2; Viral Nonstructural Proteins; Virus Replication; HEK293 Cells

PubMed: 39143215
DOI: 10.1038/s41586-024-07817-y

Review

Authors: Barth D Grant, Miyuki Sato

Studies in C. elegans have begun to reveal new components and new mechanisms associated with intracellular membrane traffic in a variety of cell types. The worm benefits from many of the advantages of yeast as a genetically tractable organism for these kinds of studies while offering the unique opportunity to probe how these pathways have been extended and modified in the context of a multicellular animal undergoing development to produce diverse cell types such as muscles, nerves, and polarized epithelia. This review summarizes recent work elucidating endocytic pathways, primarily in the worm germ line and coelomocytes, and also touches on diverse studies of secretion, especially in ectodermal cells of epithelial character.

Topics: Animals; Biological Transport; Caenorhabditis elegans; Endocytosis; Humans; Intracellular Membranes; Metabolic Networks and Pathways

PubMed: 18050485
DOI: 10.1895/wormbook.1.77.1

Review

Authors: Bernard Moss

Poxviruses differ from most DNA viruses by replicating entirely within the cytoplasm. The first discernible viral structures are crescents and spherical immature virions containing a single lipoprotein membrane bilayer with an external honeycomb lattice. Because this viral membrane displays no obvious continuity with a cellular organelle, a de novo origin was suggested. Nevertheless, transient connections between viral and cellular membranes could be difficult to resolve. Despite the absence of direct evidence, the intermediate compartment (ERGIC) between the endoplasmic reticulum (ER) and Golgi apparatus and the ER itself were considered possible sources of crescent membranes. A break-through in understanding poxvirus membrane biogenesis has come from recent studies of the abortive replication of several vaccinia virus null mutants. Novel images showing continuity between viral crescents and the ER and the accumulation of immature virions in the expanded ER lumen provide the first direct evidence for a cellular origin of this poxvirus membrane.

Topics: Animals; Endoplasmic Reticulum; Host-Pathogen Interactions; Humans; Intracellular Membranes; Poxviridae; Virus Assembly

PubMed: 25728299
DOI: 10.1016/j.virol.2015.02.003

Review

Authors: Jae-Joon Jung, Shivangi M Inamdar, Ajit Tiwari...

Intracellular membrane trafficking along endocytic and secretory transport pathways plays a critical role in diverse cellular functions including both developmental and pathological processes. Briefly, proteins and lipids destined for transport to distinct locations are collectively assembled into vesicles and delivered to their target site by vesicular fusion. SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins are required for these events, during which v-SNAREs (vesicle SNAREs) interact with t-SNAREs (target SNAREs) to allow transfer of cargo from donor vesicle to target membrane. Recently, the t-SNARE family member, syntaxin-6, has been shown to play an important role in the transport of proteins that are key to diverse cellular dynamic processes. In this paper, we briefly discuss the specific role of SNAREs in various mammalian cell types and comprehensively review the various roles of the Golgi- and endosome-localized t-SNARE, syntaxin-6, in membrane trafficking during physiological as well as pathological conditions.

Topics: Animals; Endocytosis; Endothelial Cells; Humans; Intracellular Membranes; Protein Transport; Qa-SNARE Proteins; SNARE Proteins; Secretory Vesicles

PubMed: 22489884
DOI: 10.1042/BSR20120006

Review

Authors: Stephanie E Crilly, Manojkumar A Puthenveedu

G protein-coupled receptors (GPCRs) are integral membrane proteins that transduce a wide array of inputs including light, ions, hormones, and neurotransmitters into intracellular signaling responses which underlie complex processes ranging from vision to learning and memory. Although traditionally thought to signal primarily from the cell surface, GPCRs are increasingly being recognized as capable of signaling from intracellular membrane compartments, including endosomes, the Golgi apparatus, and nuclear membranes. Remarkably, GPCR signaling from these membranes produces functional effects that are distinct from signaling from the plasma membrane, even though often the same G protein effectors and second messengers are activated. In this review, we will discuss the emerging idea of a "spatial bias" in signaling. We will present the evidence for GPCR signaling through G protein effectors from intracellular membranes, and the ways in which this signaling differs from canonical plasma membrane signaling with important implications for physiology and pharmacology. We also highlight the potential mechanisms underlying spatial bias of GPCR signaling, including how intracellular membranes and their associated lipids and proteins affect GPCR activity and signaling.

Topics: Endosomes; Intracellular Membranes; Protein Transport; Receptors, G-Protein-Coupled; Signal Transduction

PubMed: 33231722
DOI: 10.1007/s00232-020-00158-7