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Regulation of Membrane Trafficking and Its Potential Implications 2014

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

Deadline for manuscript submissions: closed (30 September 2014) | Viewed by 92909

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Prof. Dr. Jeremy Simpson

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School of Biology and Environmental Science, Science Centre - West, University College Dublin, Belfield, Dublin 4, Ireland
Interests: organisation and regulation of eukaryotic membrane traffic pathways
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In 2013, we ran a Special Issue inviting review and research articles within the area of “Regulation of Membrane Trafficking and Its Potential Implications” (https://www.mdpi.com/si/ijms/membrane-trafficking/). This issue was extremely successful. In total, we published seventeen articles, and have received a very high number of downloads. 2013 also saw the awarding of the Nobel Prize in Physiology or Medicine to three of the pioneers in the membrane traffic field, namely James Rothman, Randy Schekman, and Thomas Südhof. Therefore, with the field now being in full prominence, we have decided to run another Special Issue along the same theme this year. We would particularly welcome articles showing novel links between membrane trafficking and other cellular events, articles describing the characterization of new regulatory machinery, and short reviews giving new perspectives on the regulation of membrane trafficking processes. As before, we also welcome articles describing membrane trafficking events from a wide variety of organisms. We look forward to receiving your submissions, and hope that this Special Issue is as successful as the previous one.

Prof. Dr. Jeremy C. Simpson
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

membrane traffic
secretory pathway
endocytosis and internalization pathways
Golgi complex
coat proteins
small GTPases
lipids, phosphoinositides and membrane traffic
cytoskeleton and membrane traffic
signaling pathways and membrane traffic
disease, infection, and membrane traffic

Related Special Issue

Regulation of Membrane Trafficking and Its Potential Implications in International Journal of Molecular Sciences (17 articles)

Published Papers (10 papers)

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Research

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6875 KiB

Open AccessArticle

Targeted siRNA Screens Identify ER-to-Mitochondrial Calcium Exchange in Autophagy and Mitophagy Responses in RPE1 Cells

by Thomas D. B. MacVicar, Lilith V. J. C. Mannack, Robert M. Lees and Jon D. Lane

Int. J. Mol. Sci. 2015, 16(6), 13356-13380; https://doi.org/10.3390/ijms160613356 - 11 Jun 2015

Cited by 38 | Viewed by 12919

Abstract

Autophagy is an important stress response pathway responsible for the removal and recycling of damaged or redundant cytosolic constituents. Mitochondrial damage triggers selective mitochondrial autophagy (mitophagy), mediated by a variety of response factors including the Pink1/Parkin system. Using human retinal pigment epithelial cells stably expressing autophagy and mitophagy reporters, we have conducted parallel screens of regulators of endoplasmic reticulum (ER) and mitochondrial morphology and function contributing to starvation-induced autophagy and damage-induced mitophagy. These screens identified the ER chaperone and Ca²⁺ flux modulator, sigma non-opioid intracellular receptor 1 (SIGMAR1), as a regulator of autophagosome expansion during starvation. Screens also identified phosphatidyl ethanolamine methyl transferase (PEMT) and the IP3-receptors (IP3Rs) as mediators of Parkin-induced mitophagy. Further experiments suggested that IP3R-mediated transfer of Ca²⁺ from the ER lumen to the mitochondrial matrix via the mitochondrial Ca²⁺ uniporter (MCU) primes mitochondria for mitophagy. Importantly, recruitment of Parkin to damaged mitochondria did not require IP3R-mediated ER-to-mitochondrial Ca²⁺ transfer, but mitochondrial clustering downstream of Parkin recruitment was impaired, suggesting involvement of regulators of mitochondrial dynamics and/or transport. Our data suggest that Ca²⁺ flux between ER and mitochondria at presumed ER/mitochondrial contact sites is needed both for starvation-induced autophagy and for Parkin-mediated mitophagy, further highlighting the importance of inter-organellar communication for effective cellular homeostasis. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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3708 KiB

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Trans-Membrane Area Asymmetry Controls the Shape of Cellular Organelles

by Galina V. Beznoussenko, Sergei S. Pilyugin, Willie J. C. Geerts, Michael M. Kozlov, Koert N. J. Burger, Alberto Luini, Jure Derganc and Alexander A. Mironov

Int. J. Mol. Sci. 2015, 16(3), 5299-5333; https://doi.org/10.3390/ijms16035299 - 09 Mar 2015

Cited by 13 | Viewed by 6047

Abstract

Membrane organelles often have complicated shapes and differ in their volume, surface area and membrane curvature. The ratio between the surface area of the cytosolic and luminal leaflets (trans-membrane area asymmetry (TAA)) determines the membrane curvature within different sites of the organelle. Thus, the shape of the organelle could be critically dependent on TAA. Here, using mathematical modeling and stereological measurements of TAA during fast transformation of organelle shapes, we present evidence that suggests that when organelle volume and surface area are constant, TAA can regulate transformation of the shape of the Golgi apparatus, endosomal multivesicular bodies, and microvilli of brush borders of kidney epithelial cells. Extraction of membrane curvature by small spheres, such as COPI-dependent vesicles within the Golgi (extraction of positive curvature), or by intraluminal vesicles within endosomes (extraction of negative curvature) controls the shape of these organelles. For instance, Golgi tubulation is critically dependent on the fusion of COPI vesicles with Golgi cisternae, and vice versa, for the extraction of membrane curvature into 50–60 nm vesicles, to induce transformation of Golgi tubules into cisternae. Also, formation of intraluminal ultra-small vesicles after fusion of endosomes allows equilibration of their TAA, volume and surface area. Finally, when microvilli of the brush border are broken into vesicles and microvilli fragments, TAA of these membranes remains the same as TAA of the microvilli. Thus, TAA has a significant role in transformation of organelle shape when other factors remain constant. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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Open AccessArticle

Dysfunction of Endocytic Kinase AAK1 in ALS

by Bingxing Shi, Sean D. Conner and Jian Liu

Int. J. Mol. Sci. 2014, 15(12), 22918-22932; https://doi.org/10.3390/ijms151222918 - 10 Dec 2014

Cited by 30 | Viewed by 6931

Abstract

Mechanisms of human mutant superoxide dismutase 1 (SOD1)-induced toxicity in causing the familial form of amyotrophic lateral sclerosis (ALS) remain elusive. Identification of new proteins that can selectively interact with mutant SOD1s and investigation of their potential roles in ALS are important to discover new pathways that are involved in disease pathology. Using the yeast two-hybrid system, we identified the adaptor-associated kinase 1 (AAK1), a regulatory protein in clathrin-coated vesicle endocytic pathway that selectively interacted with the mutant but not the wild-type SOD1. Using both transgenic mouse and rat SOD1-linked familial ALS (FALS) models, we found that AAK1 was partially colocalized with the endosomal and presynaptic protein markers under the normal physiological condition, but was mislocated into aggregates that contained mutant SOD1s and the neurofilament proteins in rodent models of ALS in disease. AAK1 protein levels were also decreased in ALS patients. These results suggest that dysfunction of a component in the endosomal and synaptic vesicle recycling pathway is involved in ALS pathology. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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4521 KiB

Open AccessArticle

An Uncleaved Signal Peptide Directs the Malus xiaojinensis Iron Transporter Protein Mx IRT1 into the ER for the PM Secretory Pathway

by Peng Zhang, Song Tan, James O. Berry, Peng Li, Na Ren, Shuang Li, Guang Yang, Wei-Bing Wang, Xiao-Ting Qi and Li-Ping Yin

Int. J. Mol. Sci. 2014, 15(11), 20413-20433; https://doi.org/10.3390/ijms151120413 - 07 Nov 2014

Cited by 12 | Viewed by 9809

Abstract

Malus xiaojinensis iron-regulated transporter 1 (Mx IRT1) is a highly effective inducible iron transporter in the iron efficient plant Malus xiaojinensis. As a multi-pass integral plasma membrane (PM) protein, Mx IRT1 is predicted to consist of eight transmembrane domains, with a putative N-terminal signal peptide (SP) of 1–29 amino acids. To explore the role of the putative SP, constructs expressing Mx IRT1 (with an intact SP) and Mx DsIRT1 (with a deleted SP) were prepared for expression in Arabidopsis and in yeast. Mx IRT1 could rescue the iron-deficiency phenotype of an Arabidopsis irt1 mutant, and complement the iron-limited growth defect of the yeast mutant DEY 1453 (fet3fet4). Furthermore, fluorescence analysis indicated that a chimeric Mx IRT1-eGFP (enhanced Green Fluorescent Protein) construct was translocated into the ER (Endoplasmic reticulum) for the PM sorting pathway. In contrast, the SP-deleted Mx DsIRT1 could not rescue either of the mutant phenotypes, nor direct transport of the GFP signal into the ER. Interestingly, immunoblot analysis indicated that the SP was not cleaved from the mature protein following transport into the ER. Taken together, data presented here provides strong evidence that an uncleaved SP determines ER-targeting of Mx IRT1 during the initial sorting stage, thereby enabling the subsequent transport and integration of this protein into the PM for its crucial role in iron uptake. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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749 KiB

Open AccessArticle

The Critical Role of Membrane Cholesterol in Salmonella-Induced Autophagy in Intestinal Epithelial Cells

by Fu-Chen Huang

Int. J. Mol. Sci. 2014, 15(7), 12558-12572; https://doi.org/10.3390/ijms150712558 - 15 Jul 2014

Cited by 18 | Viewed by 6391

Abstract

It was previously observed that plasma membrane cholesterol plays a critical role in the Salmonella-induced phosphatidylinositol 3-kinase-dependent (PI3K)-dependent anti-inflammatory response in intestinal epithelial cells (IECs). The PI3K/Akt pathway is associated with autophagy which has emerged as a critical mechanism of host defense against several intracellular bacterial pathogens. Plasma membrane contributes directly to the formation of early Atg16L1-positive autophagosome precursors. Therefore, this study aimed to investigate the role of plasma membrane cholesterol on the Salmonella-induced autophagy in IECs. By using methyl-beta-cyclodextrin (MBCD), it was demonstrated that disruption of membrane cholesterol by MBCD enhanced NOD2 and Atg16L1 proteins expression in membrane, and autophagic LC3II proteins expression and LC3 punctae in Salmonella-infected Caco-2 cells, which was counteracted by Atg16L1 siRNA. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) siRNA enhanced the Salmonella-induced activation of Akt in Caco-2 cells. However, inhibitors of Akt or extracellular signal-regulated kinases (ERK) had no significant effect on Salmonella-induced autophagy Beclin 1 or LC3 proteins expression. In conclusion, our study suggests that cholesterol accumulation in the plasma membrane at the entry site of Salmonella results in the formation of Salmonella-containing vacuole (SCV) and decreased autophagy. Our results offer mechanistic insights on the critical role of membrane cholesterol in the pathogenesis of Salmonella infection in intestinal epithelial cells and the therapeutic potential of its antagonists. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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Review

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883 KiB

Open AccessReview

Ligand-Induced Dynamics of Neurotrophin Receptors Investigated by Single-Molecule Imaging Approaches

by Laura Marchetti, Stefano Luin, Fulvio Bonsignore, Teresa De Nadai, Fabio Beltram and Antonino Cattaneo

Int. J. Mol. Sci. 2015, 16(1), 1949-1979; https://doi.org/10.3390/ijms16011949 - 16 Jan 2015

Cited by 13 | Viewed by 7808

Abstract

Neurotrophins are secreted proteins that regulate neuronal development and survival, as well as maintenance and plasticity of the adult nervous system. The biological activity of neurotrophins stems from their binding to two membrane receptor types, the tropomyosin receptor kinase and the p75 neurotrophin receptors (NRs). The intracellular signalling cascades thereby activated have been extensively investigated. Nevertheless, a comprehensive description of the ligand-induced nanoscale details of NRs dynamics and interactions spanning from the initial lateral movements triggered at the plasma membrane to the internalization and transport processes is still missing. Recent advances in high spatio-temporal resolution imaging techniques have yielded new insight on the dynamics of NRs upon ligand binding. Here we discuss requirements, potential and practical implementation of these novel approaches for the study of neurotrophin trafficking and signalling, in the framework of current knowledge available also for other ligand-receptor systems. We shall especially highlight the correlation between the receptor dynamics activated by different neurotrophins and the respective signalling outcome, as recently revealed by single-molecule tracking of NRs in living neuronal cells. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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1032 KiB

Open AccessReview

Membrane Trafficking in the Yeast Saccharomyces cerevisiae Model

by Serge Feyder, Johan-Owen De Craene, Séverine Bär, Dimitri L. Bertazzi and Sylvie Friant

Int. J. Mol. Sci. 2015, 16(1), 1509-1525; https://doi.org/10.3390/ijms16011509 - 09 Jan 2015

Cited by 101 | Viewed by 14935

Abstract

The yeast Saccharomyces cerevisiae is one of the best characterized eukaryotic models. The secretory pathway was the first trafficking pathway clearly understood mainly thanks to the work done in the laboratory of Randy Schekman in the 1980s. They have isolated yeast sec mutants unable to secrete an extracellular enzyme and these SEC genes were identified as encoding key effectors of the secretory machinery. For this work, the 2013 Nobel Prize in Physiology and Medicine has been awarded to Randy Schekman; the prize is shared with James Rothman and Thomas Südhof. Here, we present the different trafficking pathways of yeast S. cerevisiae. At the Golgi apparatus newly synthesized proteins are sorted between those transported to the plasma membrane (PM), or the external medium, via the exocytosis or secretory pathway (SEC), and those targeted to the vacuole either through endosomes (vacuolar protein sorting or VPS pathway) or directly (alkaline phosphatase or ALP pathway). Plasma membrane proteins can be internalized by endocytosis (END) and transported to endosomes where they are sorted between those targeted for vacuolar degradation and those redirected to the Golgi (recycling or RCY pathway). Studies in yeast S. cerevisiae allowed the identification of most of the known effectors, protein complexes, and trafficking pathways in eukaryotic cells, and most of them are conserved among eukaryotes. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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2153 KiB

Open AccessReview

ESCRT Function in Cytokinesis: Location, Dynamics and Regulation by Mitotic Kinases

by Musab S. Bhutta, Christopher J. McInerny and Gwyn W. Gould

Int. J. Mol. Sci. 2014, 15(12), 21723-21739; https://doi.org/10.3390/ijms151221723 - 25 Nov 2014

Cited by 25 | Viewed by 9311

Abstract

Mammalian cytokinesis proceeds by constriction of an actomyosin ring and furrow ingression, resulting in the formation of the midbody bridge connecting two daughter cells. At the centre of the midbody resides the Flemming body, a dense proteinaceous ring surrounding the interlocking ends of anti-parallel microtubule arrays. Abscission, the terminal step of cytokinesis, occurs near the Flemming body. A series of broad processes govern abscission: the initiation and stabilisation of the abscission zone, followed by microtubule severing and membrane scission—The latter mediated by the endosomal sorting complex required for transport (ESCRT) proteins. A key goal of cell and developmental biologists is to develop a clear understanding of the mechanisms that underpin abscission, and how the spatiotemporal coordination of these events with previous stages in cell division is accomplished. This article will focus on the function and dynamics of the ESCRT proteins in abscission and will review recent work, which has begun to explore how these complex protein assemblies are regulated by the cell cycle machinery. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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833 KiB

Open AccessReview

Molecular Mechanisms for the Regulation of Insulin-Stimulated Glucose Uptake by Small Guanosine Triphosphatases in Skeletal Muscle and Adipocytes

by Takaya Satoh

Int. J. Mol. Sci. 2014, 15(10), 18677-18692; https://doi.org/10.3390/ijms151018677 - 16 Oct 2014

Cited by 80 | Viewed by 8272

Abstract

Insulin is a hormone that regulates the blood glucose level by stimulating various physiological responses in its target tissues. In skeletal muscle and adipose tissue, insulin promotes membrane trafficking of the glucose transporter GLUT4 from GLUT4 storage vesicles to the plasma membrane, thereby facilitating the uptake of glucose from the circulation. Detailed mechanisms underlying insulin-dependent intracellular signal transduction for glucose uptake remain largely unknown. In this article, I give an overview on the recently identified signaling network involving Rab, Ras, and Rho family small guanosine triphosphatases (GTPases) that regulates glucose uptake in insulin-responsive tissues. In particular, the regulatory mechanisms for these small GTPases and the cross-talk between protein kinase and small GTPase cascades are highlighted. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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613 KiB

Open AccessReview

The Roles of Monomeric GTP-Binding Proteins in Macroautophagy in Saccharomyces cerevisiae

by Shu Yang and Anne G. Rosenwald

Int. J. Mol. Sci. 2014, 15(10), 18084-18101; https://doi.org/10.3390/ijms151018084 - 09 Oct 2014

Cited by 7 | Viewed by 9773

Abstract

Autophagy is a cellular degradation process that sequesters components into a double-membrane structure called the autophagosome, which then fuses with the lysosome or vacuole for hydrolysis and recycling of building blocks. Bulk phase autophagy, also known as macroautophagy, controlled by specific Atg proteins, can be triggered by a variety of stresses, including starvation. Because autophagy relies extensively on membrane traffic to form the membranous structures, factors that control membrane traffic are essential for autophagy. Among these factors, the monomeric GTP-binding proteins that cycle between active and inactive conformations form an important group. In this review, we summarize the functions of the monomeric GTP-binding proteins in autophagy, especially with reference to experiments in Saccharomyces cerevisiae. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications 2014)

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