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Intracellular Membrane Transport: Models and Machines

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 24994

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Istituto FIRC di Oncologia Molecolare (IFOM-IEO Campus), Via Adamello 16, 20139 Milan, Italy
Interests: intracellular transport Golgi complex; endothelium, atherosclerosis; electron microscopy
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Special Issue Information

Tremendous progress in the deciphering of the molecular mechanisms of intracellular membrane transport (ICMT; 2013 Nobel Prize) makes necessary re-evaluation of these data in tern of cell physiology, not only in cell culture but also in organs, organisms and organoids. Moreover, the current situation in this field is extremely unclear: it is enough to say that at least four different textbook models of ICMT at different stages are seriously considered. Therefore, the analysis of all these models, all steps of ICMT and most molecular machines in one issue could represent an important move towards understanding this field. Such a collection of modern data from the established scientists of the world with different points of view would create the welcome possibility for the evaluation of these contradictions and aid in the search for correct models. We plan to collect modern data from active scientists in the field.

Prof. Dr. Alexandre Mironov
Guest Editor

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Keywords

  • Intracellular transport
  • Golgi complex
  • Golgi apparatus
  • Coatomer
  • COP
  • Clathrin
  • SNARE
  • Rab
  • GLycosylation enzymes
  • Nuclear sugar transporters
  • GTPase
  • Endosome
  • Endoplasmic reticulum
  • Exit site

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Published Papers (8 papers)

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Editorial

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3 pages, 177 KiB  
Editorial
Understanding the Golgi Apparatus and Intracellular Transport Pathways
by Alexander A. Mironov
Int. J. Mol. Sci. 2023, 24(8), 7549; https://doi.org/10.3390/ijms24087549 - 20 Apr 2023
Viewed by 1352
Abstract
Today, the future paradigm of intracellular transport could be based on four competing models, namely the vesicular model, the cisterna maturation–progression model, the diffusion model, and the kiss-and-run model [...] Full article
(This article belongs to the Special Issue Intracellular Membrane Transport: Models and Machines)

Research

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41 pages, 5162 KiB  
Article
The Diffusion Model of Intra-Golgi Transport Has Limited Power
by Galina V. Beznoussenko, Andrei Iu. Bejan, Seetharaman Parashuraman, Alberto Luini, Hee-Seok Kweon and Alexander A. Mironov
Int. J. Mol. Sci. 2023, 24(2), 1375; https://doi.org/10.3390/ijms24021375 - 10 Jan 2023
Cited by 5 | Viewed by 2344
Abstract
The Golgi complex (GC) is the main station along the cell biosecretory pathway. Until now, mechanisms of intra-Golgi transport (IGT) have remained unclear. Herein, we confirm that the goodness-of-fit of the regression lines describing the exit of a cargo from the Golgi zone [...] Read more.
The Golgi complex (GC) is the main station along the cell biosecretory pathway. Until now, mechanisms of intra-Golgi transport (IGT) have remained unclear. Herein, we confirm that the goodness-of-fit of the regression lines describing the exit of a cargo from the Golgi zone (GZ) corresponds to an exponential decay. When the GC was empty before the re-initiation of the intra-Golgi transport, this parameter of the curves describing the kinetics of different cargoes (which are deleted in Golgi vesicles) with different diffusional mobilities within the GZ as well as their exit from the GZ was maximal for the piecewise nonlinear regression, wherein the first segment was horizontal, while the second segment was similar to the exponential decay. The kinetic curve describing cargo exit from the GC per se resembled a linear decay. The Monte-Carlo simulation revealed that such curves reflect the role of microtubule growth in cells with a central GC or the random hovering of ministacks in cells lacking a microtubule. The synchronization of cargo exit from the GC already filled with a cargo using the wave synchronization protocol did not reveal the equilibration of cargo within a Golgi stack, which would be expected from the diffusion model (DM) of IGT. Moreover, not all cisternae are connected to each other in mini-stacks that are transporting membrane proteins. Finally, the kinetics of post-Golgi carriers and the important role of SNAREs for IGT at different level of IGT also argue against the DM of IGT. Full article
(This article belongs to the Special Issue Intracellular Membrane Transport: Models and Machines)
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18 pages, 3167 KiB  
Article
Divergent Contribution of the Golgi Apparatus to Microtubule Organization in Related Cell Lines
by Ilya B. Brodsky, Artem I. Fokin, Aleksei A. Efremov, Elena S. Nadezhdina and Anton V. Burakov
Int. J. Mol. Sci. 2022, 23(24), 16178; https://doi.org/10.3390/ijms232416178 - 19 Dec 2022
Cited by 1 | Viewed by 2440
Abstract
Membrane trafficking in interphase animal cells is accomplished mostly along the microtubules. Microtubules are often organized radially by the microtubule-organizing center to coordinate intracellular transport. Along with the centrosome, the Golgi often serves as a microtubule-organizing center, capable of nucleating and retaining microtubules. [...] Read more.
Membrane trafficking in interphase animal cells is accomplished mostly along the microtubules. Microtubules are often organized radially by the microtubule-organizing center to coordinate intracellular transport. Along with the centrosome, the Golgi often serves as a microtubule-organizing center, capable of nucleating and retaining microtubules. Recent studies revealed the role of a special subset of Golgi-derived microtubules, which facilitates vesicular traffic from this central transport hub of the cell. However, proteins essential for microtubule organization onto the Golgi might be differentially expressed in different cell lines, while many potential participants remain undiscovered. In the current work, we analyzed the involvement of the Golgi complex in microtubule organization in related cell lines. We studied two cell lines, both originating from green monkey renal epithelium, and found that they relied either on the centrosome or on the Golgi as a main microtubule-organizing center. We demonstrated that the difference in their Golgi microtubule-organizing activity was not associated with the well-studied proteins, such as CAMSAP3, CLASP2, GCC185, and GMAP210, but revealed several potential candidates involved in this process. Full article
(This article belongs to the Special Issue Intracellular Membrane Transport: Models and Machines)
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43 pages, 8458 KiB  
Article
Comparison of the Cisterna Maturation-Progression Model with the Kiss-and-Run Model of Intra-Golgi Transport: Role of Cisternal Pores and Cargo Domains
by Galina V. Beznoussenko, Hee-Seok Kweon, Irina S. Sesorova and Alexander A. Mironov
Int. J. Mol. Sci. 2022, 23(7), 3590; https://doi.org/10.3390/ijms23073590 - 25 Mar 2022
Cited by 9 | Viewed by 3266
Abstract
The Golgi complex is the central station of the secretory pathway. Knowledge about the mechanisms of intra-Golgi transport is inconsistent. Here, we compared the explanatory power of the cisterna maturation-progression model and the kiss-and-run model. During intra-Golgi transport, conventional cargoes undergo concentration and [...] Read more.
The Golgi complex is the central station of the secretory pathway. Knowledge about the mechanisms of intra-Golgi transport is inconsistent. Here, we compared the explanatory power of the cisterna maturation-progression model and the kiss-and-run model. During intra-Golgi transport, conventional cargoes undergo concentration and form cisternal distensions or distinct membrane domains that contain only one membrane cargo. These domains and distension are separated from the rest of the Golgi cisternae by rows of pores. After the arrival of any membrane cargo or a large cargo aggregate at the Golgi complex, the cis-Golgi SNAREs become enriched within the membrane of cargo-containing domains and then replaced by the trans-Golgi SNAREs. During the passage of these domains, the number of cisternal pores decreases. Restoration of the cisternal pores is COPI-dependent. Our observations are more in line with the kiss-and-run model. Full article
(This article belongs to the Special Issue Intracellular Membrane Transport: Models and Machines)
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Review

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21 pages, 6317 KiB  
Review
The Regulated Secretion and Models of Intracellular Transport: The Goblet Cell as an Example
by Alexander A. Mironov and Galina V. Beznoussenko
Int. J. Mol. Sci. 2023, 24(11), 9560; https://doi.org/10.3390/ijms24119560 - 31 May 2023
Cited by 4 | Viewed by 1588
Abstract
Transport models are extremely important to map thousands of proteins and their interactions inside a cell. The transport pathways of luminal and at least initially soluble secretory proteins synthesized in the endoplasmic reticulum can be divided into two groups: the so-called constitutive secretory [...] Read more.
Transport models are extremely important to map thousands of proteins and their interactions inside a cell. The transport pathways of luminal and at least initially soluble secretory proteins synthesized in the endoplasmic reticulum can be divided into two groups: the so-called constitutive secretory pathway and regulated secretion (RS) pathway, in which the RS proteins pass through the Golgi complex and are accumulated into storage/secretion granules (SGs). Their contents are released when stimuli trigger the fusion of SGs with the plasma membrane (PM). In specialized exocrine, endocrine, and nerve cells, the RS proteins pass through the baso-lateral plasmalemma. In polarized cells, the RS proteins secrete through the apical PM. This exocytosis of the RS proteins increases in response to external stimuli. Here, we analyze RS in goblet cells to try to understand the transport model that can be used for the explanation of the literature data related to the intracellular transport of their mucins. Full article
(This article belongs to the Special Issue Intracellular Membrane Transport: Models and Machines)
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38 pages, 6651 KiB  
Review
Intracellular Membrane Transport in Vascular Endothelial Cells
by Alexander A. Mironov, Anna Mironov, Barbara Sanavio, Silke Krol and Galina V. Beznoussenko
Int. J. Mol. Sci. 2023, 24(6), 5791; https://doi.org/10.3390/ijms24065791 - 17 Mar 2023
Cited by 7 | Viewed by 2971
Abstract
The main component of blood and lymphatic vessels is the endothelium covering their luminal surface. It plays a significant role in many cardiovascular diseases. Tremendous progress has been made in deciphering of molecular mechanisms involved into intracellular transport. However, molecular machines are mostly [...] Read more.
The main component of blood and lymphatic vessels is the endothelium covering their luminal surface. It plays a significant role in many cardiovascular diseases. Tremendous progress has been made in deciphering of molecular mechanisms involved into intracellular transport. However, molecular machines are mostly characterized in vitro. It is important to adapt this knowledge to the situation existing in tissues and organs. Moreover, contradictions have accumulated within the field related to the function of endothelial cells (ECs) and their trans-endothelial pathways. This has induced necessity for the re-evaluation of several mechanisms related to the function of vascular ECs and intracellular transport and transcytosis there. Here, we analyze available data related to intracellular transport within ECs and re-examine several hypotheses about the role of different mechanisms in transcytosis across ECs. We propose a new classification of vascular endothelium and hypotheses related to the functional role of caveolae and mechanisms of lipid transport through ECs. Full article
(This article belongs to the Special Issue Intracellular Membrane Transport: Models and Machines)
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24 pages, 1383 KiB  
Review
COVID-19 Biogenesis and Intracellular Transport
by Alexander A. Mironov, Maksim A. Savin and Galina V. Beznoussenko
Int. J. Mol. Sci. 2023, 24(5), 4523; https://doi.org/10.3390/ijms24054523 - 24 Feb 2023
Cited by 8 | Viewed by 2720
Abstract
SARS-CoV-2 is responsible for the COVID-19 pandemic. The structure of SARS-CoV-2 and most of its proteins of have been deciphered. SARS-CoV-2 enters cells through the endocytic pathway and perforates the endosomes’ membranes, and its (+) RNA appears in the cytosol. Then, SARS-CoV-2 starts [...] Read more.
SARS-CoV-2 is responsible for the COVID-19 pandemic. The structure of SARS-CoV-2 and most of its proteins of have been deciphered. SARS-CoV-2 enters cells through the endocytic pathway and perforates the endosomes’ membranes, and its (+) RNA appears in the cytosol. Then, SARS-CoV-2 starts to use the protein machines of host cells and their membranes for its biogenesis. SARS-CoV-2 generates a replication organelle in the reticulo-vesicular network of the zippered endoplasmic reticulum and double membrane vesicles. Then, viral proteins start to oligomerize and are subjected to budding within the ER exit sites, and its virions are passed through the Golgi complex, where the proteins are subjected to glycosylation and appear in post-Golgi carriers. After their fusion with the plasma membrane, glycosylated virions are secreted into the lumen of airways or (seemingly rarely) into the space between epithelial cells. This review focuses on the biology of SARS-CoV-2’s interactions with cells and its transport within cells. Our analysis revealed a significant number of unclear points related to intracellular transport in SARS-CoV-2-infected cells. Full article
(This article belongs to the Special Issue Intracellular Membrane Transport: Models and Machines)
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18 pages, 1921 KiB  
Review
Interactions of Lipid Droplets with the Intracellular Transport Machinery
by Selma Yilmaz Dejgaard and John F. Presley
Int. J. Mol. Sci. 2021, 22(5), 2776; https://doi.org/10.3390/ijms22052776 - 9 Mar 2021
Cited by 14 | Viewed by 7330
Abstract
Historically, studies of intracellular membrane trafficking have focused on the secretory and endocytic pathways and their major organelles. However, these pathways are also directly implicated in the biogenesis and function of other important intracellular organelles, the best studied of which are peroxisomes and [...] Read more.
Historically, studies of intracellular membrane trafficking have focused on the secretory and endocytic pathways and their major organelles. However, these pathways are also directly implicated in the biogenesis and function of other important intracellular organelles, the best studied of which are peroxisomes and lipid droplets. There is a large recent body of work on these organelles, which have resulted in the introduction of new paradigms regarding the roles of membrane trafficking organelles. In this review, we discuss the roles of membrane trafficking in the life cycle of lipid droplets. This includes the complementary roles of lipid phase separation and proteins in the biogenesis of lipid droplets from endoplasmic reticulum (ER) membranes, and the attachment of mature lipid droplets to membranes by lipidic bridges and by more conventional protein tethers. We also discuss the catabolism of neutral lipids, which in part results from the interaction of lipid droplets with cytosolic molecules, but with important roles for both macroautophagy and microautophagy. Finally, we address their eventual demise, which involves interactions with the autophagocytotic machinery. We pay particular attention to the roles of small GTPases, particularly Rab18, in these processes. Full article
(This article belongs to the Special Issue Intracellular Membrane Transport: Models and Machines)
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