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Physical Biology Sep 2019The Golgi apparatus has intrigued researchers since its discovery and despite the advances, there are still many open questions in regards to its shape and function. We...
The Golgi apparatus has intrigued researchers since its discovery and despite the advances, there are still many open questions in regards to its shape and function. We propose a mechanical model of Golgi apparatus stack and explain its most elementary geometrical properties: the equilibrium number of cisternae, the stack size, and its general equilibrium shape. Combining both analytical and numerical methods we successfully reconstruct the stack morphology within the theory of bending elasticity. We demonstrate that energy-wise the stack prefers an overall bent shape and show strong evidence that the adhesion strength determines the equilibrium number of cisternae per stack. We explore the morphological role of fenestrations and discuss their impact on the overall stack structure. We also comment on the effects of the asymmetry in the composition of membrane leaflets on the shape of the cisternae and thus offer a broad steady-state study of the stack morphology and present a method that can be used also for other membrane-bound organelles.
Topics: Biomechanical Phenomena; Elasticity; Golgi Apparatus; Models, Biological
PubMed: 31365910
DOI: 10.1088/1478-3975/ab3766 -
Current Opinion in Cell Biology Feb 2020Membrane trafficking plays a crucial role in cell polarity by directing lipids and proteins to specific subcellular locations in the cell and sustaining a polarized... (Review)
Review
Membrane trafficking plays a crucial role in cell polarity by directing lipids and proteins to specific subcellular locations in the cell and sustaining a polarized state. The Golgi apparatus, the master organizer of membrane trafficking, can be subdivided into three layers that play different mechanical roles: a cytoskeletal layer, the so-called Golgi matrix, and the Golgi membranes. First, the outer regions of the Golgi apparatus interact with cytoskeletal elements, mainly actin and microtubules, which shape, position, and orient the organelle. Closer to the Golgi membranes, a matrix of long coiled-coiled proteins not only selectively captures transport intermediates but also participates in signaling events during polarization of membrane trafficking. Finally, the Golgi membranes themselves serve as active signaling platforms during cell polarity events. We review here the recent findings that link the Golgi apparatus to cell polarity, focusing on the roles of the cytoskeleton, the Golgi matrix, and the Golgi membranes.
Topics: Cell Movement; Cell Polarity; Cytoskeleton; Golgi Apparatus; Humans; Microtubules
PubMed: 31751898
DOI: 10.1016/j.ceb.2019.10.003 -
BioFactors (Oxford, England) Nov 2021The organelle of eukaryotes is a finely regulated system. Once disturbed, it activates the specific autoregulatory systems, namely, organelle autoregulation. Among... (Review)
Review
The organelle of eukaryotes is a finely regulated system. Once disturbed, it activates the specific autoregulatory systems, namely, organelle autoregulation. Among which, the Golgi stress response accounts for one. When the abundance and capacity of the Golgi apparatus are insufficient compared with cellular demand, the Golgi stress response is activated to enhance the function of the Golgi apparatus. Although the molecular mechanism of the Golgi stress response has not been well characterized yet, it seems to be an important part of the mammalian stress response. In this review, we discuss the current status of research on the six pathways of the mammalian Golgi stress response (the TFE3, heat shock protein 47, CREB3, E26 transformation specific, proteoglycan, and mucin pathways), which regulate the general function of the Golgi apparatus, anti-apoptosis, pro-apoptosis, proteoglycan glycosylation, and mucin glycosylation, respectively.
Topics: Golgi Apparatus; HeLa Cells; Homeostasis; Humans; Mucins; Stress, Physiological
PubMed: 34500494
DOI: 10.1002/biof.1780 -
Biochemical Society Transactions Jun 2020Glycosyltransferases are a large family of enzymes responsible for covalently linking sugar monosaccharides to a variety of organic substrates. These enzymes drive the... (Review)
Review
Glycosyltransferases are a large family of enzymes responsible for covalently linking sugar monosaccharides to a variety of organic substrates. These enzymes drive the synthesis of complex oligosaccharides known as glycans, which play key roles in inter-cellular interactions across all the kingdoms of life; they also catalyze sugar attachment during the synthesis of small-molecule metabolites such as plant flavonoids. A given glycosyltransferase enzyme is typically responsible for attaching a specific donor monosaccharide, via a specific glycosidic linkage, to a specific moiety on the acceptor substrate. However these enzymes are often promiscuous, able catalyze linkages between a variety of donors and acceptors. In this review we discuss distinct classes of glycosyltransferase promiscuity, each illustrated by enzymatic examples from small-molecule or glycan synthesis. We highlight the physical causes of promiscuity, and its biochemical consequences. Structural studies of glycosyltransferases involved in glycan synthesis show that they make specific contacts with 'recognition motifs' that are much smaller than the full oligosaccharide substrate. There is a wide range in the sizes of glycosyltransferase recognition motifs: highly promiscuous enzymes recognize monosaccharide or disaccharide motifs across multiple oligosaccharides, while highly specific enzymes recognize large, complex motifs found on few oligosaccharides. In eukaryotes, the localization of glycosyltransferases within compartments of the Golgi apparatus may play a role in mitigating the glycan variability caused by enzyme promiscuity.
Topics: Amino Acid Motifs; Carbohydrates; Catalysis; Eukaryota; Glycosides; Glycosylation; Glycosyltransferases; Golgi Apparatus; Kinetics; Models, Molecular; Monosaccharides; Oligosaccharides; Polysaccharides; Substrate Specificity
PubMed: 32539082
DOI: 10.1042/BST20190651 -
Biochimica Et Biophysica Acta. General... Nov 2020The Conserved Oligomeric Golgi (COG) complex, a multi-subunit vesicle tethering complex of the CATCHR (Complexes Associated with Tethering Containing Helical Rods)... (Review)
Review
The Conserved Oligomeric Golgi (COG) complex, a multi-subunit vesicle tethering complex of the CATCHR (Complexes Associated with Tethering Containing Helical Rods) family, controls several aspects of cellular homeostasis by orchestrating retrograde vesicle traffic within the Golgi. The COG complex interacts with all key players regulating intra-Golgi trafficking, namely SNAREs, SNARE-interacting proteins, Rabs, coiled-coil tethers, and vesicular coats. In cells, COG deficiencies result in the accumulation of non-tethered COG-complex dependent (CCD) vesicles, dramatic morphological and functional abnormalities of the Golgi and endosomes, severe defects in N- and O- glycosylation, Golgi retrograde trafficking, sorting and protein secretion. In humans, COG mutations lead to severe multi-systemic diseases known as COG-Congenital Disorders of Glycosylation (COG-CDG). In this report, we review the current knowledge of the COG complex and analyze COG-related trafficking and glycosylation defects in COG-CDG patients.
Topics: Adaptor Proteins, Vesicular Transport; Animals; Biological Transport; Congenital Disorders of Glycosylation; Glycosylation; Golgi Apparatus; Humans; Multiprotein Complexes; Mutation; Protein Interaction Maps; Protein Subunits
PubMed: 32730773
DOI: 10.1016/j.bbagen.2020.129694 -
Methods in Molecular Biology (Clifton,... 2023Immunofluorescence is a technique that uses antibodies and fluorophores to label structures inside cells. The cells are normally fixed and permeabilized, and then...
Immunofluorescence is a technique that uses antibodies and fluorophores to label structures inside cells. The cells are normally fixed and permeabilized, and then structures are labelled using primary antibodies directly conjugated to fluorophores, or, more commonly, first with an antibody against an antigen of interest followed by a secondary antibody conjugated to a fluorophore that binds to the primary antibody. Fluorescence can be visualized using widefield, confocal, or super-resolution microscopy. Here we focus on labelling of the Golgi apparatus and show that different fixation and permeabilization conditions can significantly affect labelling of Golgi proteins and describe how to optimize fluorescent detection of Golgi proteins.
Topics: Animals; Golgi Apparatus; Microscopy, Fluorescence; Fluorescent Antibody Technique; Fluorescent Dyes; Antibodies; Microscopy, Confocal; Mammals
PubMed: 36512212
DOI: 10.1007/978-1-0716-2639-9_8 -
FEBS Letters Sep 2019
Topics: Biological Transport; Golgi Apparatus; Homeostasis; Lipids; Signal Transduction
PubMed: 31495944
DOI: 10.1002/1873-3468.13577 -
Methods in Molecular Biology (Clifton,... 2023Maintaining protein homeostasis (proteostasis) is vital to cellular and organismal health. How the Golgi apparatus, the central protein maturation and sorting station in...
Maintaining protein homeostasis (proteostasis) is vital to cellular and organismal health. How the Golgi apparatus, the central protein maturation and sorting station in the cell, manages misfolded proteins to maintain proteostasis is still poorly understood. Here we present a strategy for targeted protein unfolding at the Golgi that enables studying Golgi-related protein quality control and stress-signaling pathways. Targeted protein unfolding is induced by small molecule-based chemical biology approaches-hydrophobic tagging and the use of a destabilization domain. Imaging studies allow visualizing quality control (QC) phenotypes, such as the formation of QC carriers and Golgi-to-endoplasmic reticulum trafficking, and correlating these phenotypes with other trafficking processes.
Topics: Golgi Apparatus; Endoplasmic Reticulum; Protein Transport; Protein Unfolding
PubMed: 36512243
DOI: 10.1007/978-1-0716-2639-9_39 -
FEBS Letters Sep 2019Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are lipid APs attached to the extracellular leaflet of the plasma membrane (PM) via a glycolipid anchor. GPI-APs... (Review)
Review
Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are lipid APs attached to the extracellular leaflet of the plasma membrane (PM) via a glycolipid anchor. GPI-APs are commonly associated with cholesterol- and sphingolipid-enriched membrane microdomains. These microdomains help regulating various biological activities, by segregating different proteins and lipids in (nanoscale) membrane compartments. In fibroblasts, GPI-APs form actin- and cholesterol-dependent nanoclusters directly at the PM. In contrast, in polarized epithelial cells GPI-APs cluster in the Golgi apparatus, the major protein-sorting hub for the secretory pathway. Golgi clustering is required for the selective sorting of GPI-APs to the apical PM domain, but also regulates their organization and biological activities at the cell surface. In this review, we discuss recent advances in our understanding of the mechanism of GPI-AP sorting to the apical membrane. We focus on the roles of the protein moiety and lipids in the regulation of the clustering of GPI-APs in the Golgi apparatus.
Topics: Animals; Epithelial Cells; Golgi Apparatus; Humans; Membrane Proteins; Protein Transport
PubMed: 31400147
DOI: 10.1002/1873-3468.13573 -
Current Opinion in Cell Biology Apr 2022In eukaryotes, there is now compelling evidence that in addition to the conventional endoplasmic reticulum-Golgi secretory pathway, there are additional routes for the... (Review)
Review
In eukaryotes, there is now compelling evidence that in addition to the conventional endoplasmic reticulum-Golgi secretory pathway, there are additional routes for the export of cytoplasmic proteins with a critical role in numerous physio-pathological conditions. These alternative secretory pathways or unconventional protein secretion (UPS) start now to be molecularly dissected, and while UPS landscape appears to be governed by a striking diversity and heterogeneity of mechanisms, common principles are emerging. We review here the role of key molecular determinants as well as the role of central hubs for UPS, highlighting the plasticity and dynamic properties of membrane-bound compartments. We also describe recent findings that position UPS as an integral component of adaptive responses to cope with particular cellular needs and stresses.
Topics: Endoplasmic Reticulum; Golgi Apparatus; Protein Transport; Proteins; Secretory Pathway
PubMed: 35305454
DOI: 10.1016/j.ceb.2022.02.006