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Cellular and Molecular Life Sciences :... Sep 2015Sorting of macromolecules within the endosomal system is vital for physiological control of nutrient homeostasis, cell motility, and proteostasis. Trafficking routes... (Review)
Review
Sorting of macromolecules within the endosomal system is vital for physiological control of nutrient homeostasis, cell motility, and proteostasis. Trafficking routes that export macromolecules from the endosome via vesicle and tubule transport carriers constitute plasma membrane recycling and retrograde endosome-to-Golgi pathways. Proteins of the sorting nexin family have been discovered to function at nearly every step of endosomal transport carrier biogenesis and it is becoming increasingly clear that they form the core machineries of cargo-specific transport pathways that are closely integrated with cellular physiology. Here, we summarize recent progress in elucidating the pathways that mediate the biogenesis of endosome-derived transport carriers.
Topics: Biological Transport; Cell Membrane; Endosomes; Golgi Apparatus; Humans; Vesicular Transport Proteins
PubMed: 26022064
DOI: 10.1007/s00018-015-1935-x -
Cell Aug 2007GRASP proteins associate with the Golgi apparatus and have been implicated in the stacking of Golgi cisternae, vesicle tethering, and mitotic progression, but their...
GRASP proteins associate with the Golgi apparatus and have been implicated in the stacking of Golgi cisternae, vesicle tethering, and mitotic progression, but their specific functions are unclear. In this issue, Kinseth et al. (2007) show unexpectedly that a GRASP homolog is required for an unconventional secretory pathway that bypasses the usual route for Golgi-dependent membrane traffic.
Topics: Animals; Dictyostelium; Drosophila Proteins; Golgi Apparatus; Golgi Matrix Proteins; Membrane Proteins; Signal Transduction
PubMed: 17693251
DOI: 10.1016/j.cell.2007.07.030 -
Traffic (Copenhagen, Denmark) Aug 2018The tubular endolysosomal network is a quality control system that ensures the proper delivery of internalized receptors to specific subcellular destinations in order to... (Review)
Review
The tubular endolysosomal network is a quality control system that ensures the proper delivery of internalized receptors to specific subcellular destinations in order to maintain cellular homeostasis. Although retromer was originally described in yeast as a regulator of endosome-to-Golgi receptor recycling, mammalian retromer has emerged as a central player in endosome-to-plasma membrane recycling of a variety of receptors. Over the past decade, information regarding the mechanism by which retromer facilitates receptor trafficking has emerged, as has the identification of numerous retromer-associated molecules including the WASH complex, sorting nexins (SNXs) and TBC1d5. Moreover, the recent demonstration that several SNXs can directly interact with retromer cargo to facilitate endosome-to-Golgi retrieval has provided new insight into how these receptors are trafficked in cells. The mechanism by which SNX17 cargoes are recycled out of the endosomal system was demonstrated to involve a retromer-like complex termed the retriever, which is recruited to WASH positive endosomes through an interaction with the COMMD/CCDC22/CCDC93 (CCC) complex. Lastly, the mechanisms by which bacterial and viral pathogens highjack this complex sorting machinery in order to escape the endolysosomal system or remain hidden within the cells are beginning to emerge. In this review, we will highlight recent studies that have begun to unravel the intricacies by which the retromer and associated molecules contribute to receptor trafficking and how deregulation at this sorting domain can contribute to disease or facilitate pathogen infection.
Topics: Animals; Cell Membrane; Endosomes; Golgi Apparatus; Humans; Protein Transport; trans-Golgi Network
PubMed: 29667289
DOI: 10.1111/tra.12574 -
The FEBS Journal Jun 2023The M2 isoform of pyruvate kinase (PKM2) is abundantly expressed in various cancer cells and associated with tumorigenesis, tumour proliferation and tumour progression....
The M2 isoform of pyruvate kinase (PKM2) is abundantly expressed in various cancer cells and associated with tumorigenesis, tumour proliferation and tumour progression. However, the role of PKM2 in these oncological processes is not fully understood. In the present study, we depleted PKM2 expression using RNA interference (RNAi), which induced apoptotic cell death and was accompanied by the downregulation of GM130, giantin, and p115 in HeLa and ME-180 cervical cancer cells. The decreased expression of these proteins caused structural and functional disturbances in the Golgi apparatus, which manifested as the dispersion of the Golgi apparatus and delayed anterograde trafficking from the ER to the Golgi. The transcription factor, TFE3, which functions in the Golgi stress response, was responsible for the expression of GM130, giantin, and p115 that maintained the integrity of the organelle under normal growth conditions. In PKM2-knockdown cells, the translation of TFE3 was markedly reduced. Knockdown of TFE3 by RNAi resulted in the downregulation of GM130, giantin, and p115, dispersion of the Golgi apparatus, and apoptotic cell death, similar to those observed following PKM2 knockdown. Conversely, the exogenous expression of TFE3 in PKM2 knockdown cells partially mitigated the aforementioned effects. We also demonstrated that PKM2 bound to the 5' UTR on TFE3 mRNA and promoted translation. This study is the first to identify a new function for PKM2, which activates the basal Golgi stress response to maintain the integrity of the Golgi apparatus through the translation of TFE3 and promote cancer cell survival.
Topics: Humans; Female; Membrane Proteins; Uterine Cervical Neoplasms; HeLa Cells; Golgi Apparatus; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
PubMed: 36705569
DOI: 10.1111/febs.16740 -
FEBS Letters Sep 2019Glycans are one of the four biopolymers of the cell and they play important roles in cellular and organismal physiology. They consist of both linear and branched... (Review)
Review
Glycans are one of the four biopolymers of the cell and they play important roles in cellular and organismal physiology. They consist of both linear and branched structures and are synthesized in a nontemplated manner in the secretory pathway of mammalian cells with the Golgi apparatus playing a key role in the process. In spite of the absence of a template, the glycans synthesized by a cell are not a random collection of possible glycan structures but a distribution of specific glycans in defined quantities that is unique to each cell type (Cell type here refers to distinct cell forms present in an organism that can be distinguished based on morphological, phenotypic and/or molecular criteria.) While information to produce cell type-specific glycans is encoded in the genome, how this information is translated into cell type-specific glycome (Glycome refers to the quantitative distribution of all glycan structures present in a given cell type.) is not completely understood. We summarize here the factors that are known to influence the fidelity of glycan biosynthesis and integrate them into known glycosylation pathways so as to rationalize the translation of genetic information to cell type-specific glycome.
Topics: Animals; Genomics; Glycomics; Golgi Apparatus; Humans; Polysaccharides
PubMed: 31330561
DOI: 10.1002/1873-3468.13541 -
Cold Spring Harbor Perspectives in... Jul 2011Vesicular transport of protein and lipid cargo from the endoplasmic reticulum (ER) to cis-Golgi compartments depends on coat protein complexes, Rab GTPases, tethering... (Review)
Review
Vesicular transport of protein and lipid cargo from the endoplasmic reticulum (ER) to cis-Golgi compartments depends on coat protein complexes, Rab GTPases, tethering factors, and membrane fusion catalysts. ER-derived vesicles deliver cargo to an ER-Golgi intermediate compartment (ERGIC) that then fuses with and/or matures into cis-Golgi compartments. The forward transport pathway to cis-Golgi compartments is balanced by a retrograde directed pathway that recycles transport machinery back to the ER. How trafficking through the ERGIC and cis-Golgi is coordinated to maintain organelle structure and function is poorly understood and highlights central questions regarding trafficking routes and organization of the early secretory pathway.
Topics: COP-Coated Vesicles; Endoplasmic Reticulum; Golgi Apparatus; Membrane Fusion; Membrane Fusion Proteins; Models, Biological; Protein Structure, Tertiary; Secretory Pathway; Vesicular Transport Proteins
PubMed: 21482742
DOI: 10.1101/cshperspect.a005207 -
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 -
Cold Spring Harbor Perspectives in... Aug 2011The protein composition of the Golgi is intimately linked to its structure and function. As the Golgi serves as the major protein-sorting hub for the secretory pathway,... (Review)
Review
The protein composition of the Golgi is intimately linked to its structure and function. As the Golgi serves as the major protein-sorting hub for the secretory pathway, it faces the unique challenge of maintaining its protein composition in the face of constant influx and efflux of transient cargo proteins. Much of our understanding of how proteins are retained in the Golgi has come from studies on glycosylation enzymes, largely because of the compartment-specific distributions these proteins display. From these and other studies of Golgi membrane proteins, we now understand that a variety of retention mechanisms are employed, the majority of which involve the dynamic process of iterative rounds of retrograde and anterograde transport. Such mechanisms rely on protein conformation and amino acid-based sorting signals as well as on properties of transmembrane domains and their relationship with the unique lipid composition of the Golgi.
Topics: Golgi Apparatus; Humans; Membrane Proteins; Protein Transport
PubMed: 21525512
DOI: 10.1101/cshperspect.a005264 -
Cold Spring Harbor Perspectives in... Apr 2011Classical secretion consists of the delivery of transmembrane and soluble proteins to the plasma membrane and the extracellular medium, respectively, and is mediated by... (Review)
Review
Classical secretion consists of the delivery of transmembrane and soluble proteins to the plasma membrane and the extracellular medium, respectively, and is mediated by the organelles of the secretory pathway, the Endoplasmic Reticulum (ER), the ER exit sites, and the Golgi, as described by the Nobel Prize winner George Palade (Palade 1975). At the center of this transport route, the Golgi stack has a major role in modifying, processing, sorting, and dispatching newly synthesized proteins to their final destinations. More recently, however, it has become clear that an increasing number of transmembrane proteins reach the plasma membrane unconventionally, either by exiting the ER in non-COPII vesicles or by bypassing the Golgi. Here, we discuss the evidence for Golgi bypass and the possible physiological benefits of it. Intriguingly, at least during Drosophila development, Golgi bypass seems to be mediated by a Golgi protein, dGRASP, which is found ectopically localized to the plasma membrane.
Topics: Biological Transport; Cell Membrane; Gene Expression Regulation; Golgi Apparatus; Proteins
PubMed: 21441587
DOI: 10.1101/cshperspect.a005298 -
Histochemistry and Cell Biology Nov 2021The three-dimensional morphology of the Golgi apparatus in osteoclasts was investigated by computer-aided reconstruction. Rat femora were treated for nicotinamide...
The three-dimensional morphology of the Golgi apparatus in osteoclasts was investigated by computer-aided reconstruction. Rat femora were treated for nicotinamide adenine dinucleotide phosphatase (NADPase) cytochemistry, and light microscopy was used to select several osteoclasts in serial semi-thin sections to investigate the Golgi apparatus by backscattered electron-mode scanning electron microscopy. Lace-like structures with strong backscattered electron signals were observed around the nuclei. These structures, observed within the Golgi apparatus, were attributed to the reaction products (i.e., lead precipitates) of NADPase cytochemistry. Features on the images corresponding to the Golgi apparatus, nuclei, and ruffled border were manually traced and three-dimensionally reconstructed using ImageJ/Fiji (an open-source image processing package). In the reconstructed model, the Golgi apparatus formed an almost-continuous structure with a basket-like configuration, which surrounded all the nuclei and also partitioned them. This peculiar three-dimensional morphology of the Golgi apparatus was discovered for the first time in this study. On the basis of the location of the cis- and trans-sides of the Golgi apparatus and the reported results of previous studies, we postulated that the nuclear membrane synthesized specific proteins in the osteoclasts and, accordingly, the Golgi apparatus accumulated around the nuclei as a receptacle.
Topics: Animals; Golgi Apparatus; Histocytochemistry; Imaging, Three-Dimensional; Male; Microscopy, Electron, Scanning; NADP; Osteoclasts; Rats; Rats, Wistar
PubMed: 34436644
DOI: 10.1007/s00418-021-02024-6