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Special Issue "Membrane Transport"

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

Deadline for manuscript submissions: closed (31 January 2012)

Special Issue Editor

Guest Editor
Dr. Kip Gabriel (Website)

Department of Biochemistry & Molecular Biology, Room 253 Level 2 Building 76 (STRIP2), Monash University, Clayton, 3800, Australia
Phone: +61 3 9902 9213

Special Issue Information

Dear Colleagues,

Cells are separated from their environment by lipid membranes. The presence of membrane barriers means that mechanisms for the transport of proteins into and across membranes must also exist. In bacteria these mechanisms allow processes such as nutrient uptake, cell to cell signalling and interaction and the targeting of toxins to host cells during infection. In eukaryotic cells, the membrane system is even more elaborate with the presence of compartments, the organelles, separating biological processes. The trafficking of membrane proteins is by virtue of protein targeting signals and is dependent on machineries that can recognize them at each membrane.

The current special issue will highlight some of the most recent research in this area and provide a collection of reviews, which summarize our current understanding of the trafficking of lipids and proteins into and across cellular membranes.

Dr. Kip Gabriel
Guest Editor

Keywords

  • membranes
  • membrane proteins
  • lipids
  • proteins
  • translocase machinery
  • protein Secretion
  • organelles
  • protein targeting
  • bacterial protein secretion

Published Papers (11 papers)

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Research

Jump to: Review, Other

Open AccessArticle Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity
Int. J. Mol. Sci. 2012, 13(6), 6757-6771; doi:10.3390/ijms13066757
Received: 12 March 2012 / Revised: 16 May 2012 / Accepted: 25 May 2012 / Published: 4 June 2012
Cited by 4 | PDF Full-text (359 KB) | HTML Full-text | XML Full-text
Abstract
Multidrug resistance (MDR) is considered the main cause of cancer chemotherapy failure and patient relapse. The active drug efflux mediated by transporter proteins of the ABC (ATP-binding cassette) family is the most investigated mechanism leading to MDR. With the aim of inhibiting [...] Read more.
Multidrug resistance (MDR) is considered the main cause of cancer chemotherapy failure and patient relapse. The active drug efflux mediated by transporter proteins of the ABC (ATP-binding cassette) family is the most investigated mechanism leading to MDR. With the aim of inhibiting this transport and circumventing MDR, a great amount of work has been dedicated to identifying pharmacological inhibitors of specific ABC transporters. We recently showed that 3β-acetyl tormentic acid (3ATA) had no effect on P-gp/ABCB1 activity. Herein, we show that 3ATA strongly inhibited the activity of MRP1/ABCC1. In the B16/F10 and Ma104 cell lines, this effect was either 20X higher or similar to that observed with MK571, respectively. Nevertheless, the low inhibitory effect of 3ATA on A549, a cell line that expresses MRP1-5, suggests that it may not inhibit other MRPs. The use of cells transfected with ABCC2, ABCC3 or ABCC4 showed that 3ATA was also able to modulate these transporters, though with an inhibition ratio lower than that observed for MRP1/ABCC1. These data point to 3ATA as a new ABCC inhibitor and call attention to its potential use as a tool to investigate the function of MRP/ABCC proteins or as a co-adjuvant in the treatment of MDR tumors. Full article
(This article belongs to the Special Issue Membrane Transport)
Open AccessArticle Na+, K+-ATPase Subunit Composition in a Human Chondrocyte Cell Line; Evidence for the Presence of α1, α3, β1, β2 and β3 Isoforms
Int. J. Mol. Sci. 2012, 13(4), 5019-5034; doi:10.3390/ijms13045019
Received: 7 March 2012 / Revised: 6 April 2012 / Accepted: 12 April 2012 / Published: 20 April 2012
Cited by 2 | PDF Full-text (1217 KB) | HTML Full-text | XML Full-text
Abstract
Membrane transport systems participate in fundamental activities such as cell cycle control, proliferation, survival, volume regulation, pH maintenance and regulation of extracellular matrix synthesis. Multiple isoforms of Na+, K+-ATPase are expressed in primary chondrocytes. Some of these isoforms [...] Read more.
Membrane transport systems participate in fundamental activities such as cell cycle control, proliferation, survival, volume regulation, pH maintenance and regulation of extracellular matrix synthesis. Multiple isoforms of Na+, K+-ATPase are expressed in primary chondrocytes. Some of these isoforms have previously been reported to be expressed exclusively in electrically excitable cells (i.e., cardiomyocytes and neurons). Studying the distribution of Na+, K+-ATPase isoforms in chondrocytes makes it possible to document the diversity of isozyme pairing and to clarify issues concerning Na+, K+-ATPase isoform abundance and the physiological relevance of their expression. In this study, we investigated the expression of Na+, K+-ATPase in a human chondrocyte cell line (C-20/A4) using a combination of immunological and biochemical techniques. A panel of well-characterized antibodies revealed abundant expression of the α1, β1 and β2 isoforms. Western blot analysis of plasma membranes confirmed the above findings. Na+, K+-ATPase consists of multiple isozyme variants that endow chondrocytes with additional homeostatic control capabilities. In terms of Na+, K+-ATPase expression, the C-20/A4 cell line is phenotypically similar to primary and in situ chondrocytes. However, unlike freshly isolated chondrocytes, C-20/A4 cells are an easily accessible and convenient in vitro model for the study of Na+, K+-ATPase expression and regulation in chondrocytes. Full article
(This article belongs to the Special Issue Membrane Transport)
Open AccessArticle Expression of Transient Receptor Potential Vanilloid (TRPV) Channels in Different Passages of Articular Chondrocytes
Int. J. Mol. Sci. 2012, 13(4), 4433-4445; doi:10.3390/ijms13044433
Received: 27 February 2012 / Revised: 12 March 2012 / Accepted: 26 March 2012 / Published: 10 April 2012
Cited by 14 | PDF Full-text (395 KB) | HTML Full-text | XML Full-text
Abstract
Ion channels play important roles in chondrocyte mechanotransduction. The transient receptor potential vanilloid (TRPV) subfamily of ion channels consists of six members. TRPV1-4 are temperature sensitive calcium-permeable, relatively non-selective cation channels whereas TRPV5 and TRPV6 show high selectivity for calcium over other [...] Read more.
Ion channels play important roles in chondrocyte mechanotransduction. The transient receptor potential vanilloid (TRPV) subfamily of ion channels consists of six members. TRPV1-4 are temperature sensitive calcium-permeable, relatively non-selective cation channels whereas TRPV5 and TRPV6 show high selectivity for calcium over other cations. In this study we investigated the effect of time in culture and passage number on the expression of TRPV4, TRPV5 and TRPV6 in articular chondrocytes isolated from equine metacarpophalangeal joints. Polyclonal antibodies raised against TRPV4, TRPV5 and TRPV6 were used to compare the expression of these channels in lysates from first expansion chondrocytes (P0) and cells from passages 1–3 (P1, P2 and P3) by western blotting. TRPV4, TRPV5 and TRPV6 were expressed in all passages examined. Immunohistochemistry and immunofluorescence confirmed the presence of these channels in sections of formalin fixed articular cartilage and monolayer cultures of methanol fixed P2 chondrocytes. TRPV5 and TRPV6 were upregulated with time and passage in culture suggesting that a shift in the phenotype of the cells in monolayer culture alters the expression of these channels. In conclusion, several TRPV channels are likely to be involved in calcium signaling and homeostasis in chondrocytes. Full article
(This article belongs to the Special Issue Membrane Transport)
Open AccessArticle Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes
Int. J. Mol. Sci. 2011, 12(12), 9125-9137; doi:10.3390/ijms12129125
Received: 25 October 2011 / Revised: 10 November 2011 / Accepted: 24 November 2011 / Published: 8 December 2011
Cited by 10 | PDF Full-text (158 KB) | HTML Full-text | XML Full-text
Abstract
Channel-mediated trans-membrane chloride movement is a key process in the active cell volume regulation under osmotic stress in most cells. However, thymocytes were hypothesized to regulate their volume by activating a coupled K-Cl cotransport mechanism. Under the patch-clamp, we found that osmotic [...] Read more.
Channel-mediated trans-membrane chloride movement is a key process in the active cell volume regulation under osmotic stress in most cells. However, thymocytes were hypothesized to regulate their volume by activating a coupled K-Cl cotransport mechanism. Under the patch-clamp, we found that osmotic swelling activates two types of macroscopic anion conductance with different voltage-dependence and pharmacology. At the single-channel level, we identified two types of events: one corresponded to the maxi-anion channel, and the other one had characteristics of the volume-sensitive outwardly rectifying (VSOR) chloride channel of intermediate conductance. A VSOR inhibitor, phloretin, significantly suppressed both macroscopic VSOR-type conductance and single-channel activity of intermediate amplitude. The maxi-anion channel activity was largely suppressed by Gd3+ ions but not by phloretin. Surprisingly, [(dihydroindenyl)oxy] alkanoic acid (DIOA), a known antagonist of K-Cl cotransporter, was found to significantly suppress the activity of the VSOR-type single-channel events with no effect on the maxi-anion channels at 10 μM. The regulatory volume decrease (RVD) phase of cellular response to hypotonicity was mildly suppressed by Gd3+ ions and was completely abolished by phloretin suggesting a major impact of the VSOR chloride channel and modulatory role of the maxi-anion channel. The inhibitory effect of DIOA was also strong, and, most likely, it occurred via blocking the VSOR Cl channels. Full article
(This article belongs to the Special Issue Membrane Transport)
Open AccessArticle Tunicamycin Depresses P-Glycoprotein Glycosylation Without an Effect on Its Membrane Localization and Drug Efflux Activity in L1210 Cells
Int. J. Mol. Sci. 2011, 12(11), 7772-7784; doi:10.3390/ijms12117772
Received: 25 September 2011 / Revised: 20 October 2011 / Accepted: 3 November 2011 / Published: 10 November 2011
Cited by 15 | PDF Full-text (613 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
P-glycoprotein (P-gp), also known as ABCB1, is a member of the ABC transporter family of proteins. P-gp is an ATP-dependent drug efflux pump that is localized to the plasma membrane of mammalian cells and confers multidrug resistance in neoplastic cells. P-gp is [...] Read more.
P-glycoprotein (P-gp), also known as ABCB1, is a member of the ABC transporter family of proteins. P-gp is an ATP-dependent drug efflux pump that is localized to the plasma membrane of mammalian cells and confers multidrug resistance in neoplastic cells. P-gp is a 140-kDa polypeptide that is glycosylated to a final molecular weight of 170 kDa. Our experimental model used two variants of L1210 cells in which overexpression of P-gp was achieved: either by adaptation of parental cells (S) to vincristine (R) or by transfection with the human gene encoding P-gp (T). R and T cells were found to differ from S cells in transglycosylation reactions in our recent studies. The effects of tunicamycin on glycosylation, drug efflux activity and cellular localization of P-gp in R and T cells were examined in the present study. Treatment with tunicamycin caused less concentration-dependent cellular damage to R and T cells compared with S cells. Tunicamycin inhibited P-gp N-glycosylation in both of the P-gp-positive cells. However, tunicamycin treatment did not alter either the P-gp cellular localization to the plasma membrane or the P-gp transport activity. The present paper brings evidence that independently on the mode of P-gp expression (selection with drugs or transfection with a gene encoding P-gp) in L1210 cells, tunicamycin induces inhibition of N-glycosylation of this protein, without altering its function as plasma membrane drug efflux pump. Full article
(This article belongs to the Special Issue Membrane Transport)
Open AccessArticle Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response
Int. J. Mol. Sci. 2011, 12(9), 5815-5827; doi:10.3390/ijms12095815
Received: 29 July 2011 / Revised: 29 August 2011 / Accepted: 30 August 2011 / Published: 9 September 2011
Cited by 24 | PDF Full-text (333 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (−71T>C) gene polymorphisms were identified by TaqMan® Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p < 0.05). Conclusion: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy. Full article
(This article belongs to the Special Issue Membrane Transport)

Review

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Open AccessReview From Evolution to Pathogenesis: The Link Between β-Barrel Assembly Machineries in the Outer Membrane of Mitochondria and Gram-Negative Bacteria
Int. J. Mol. Sci. 2012, 13(7), 8038-8050; doi:10.3390/ijms13078038
Received: 1 May 2012 / Revised: 21 June 2012 / Accepted: 21 June 2012 / Published: 28 June 2012
Cited by 8 | PDF Full-text (235 KB) | HTML Full-text | XML Full-text
Abstract
β-barrel proteins are the highly abundant in the outer membranes of Gram-negative bacteria and the mitochondria in eukaryotes. The assembly of β-barrels is mediated by two evolutionary conserved machineries; the β-barrel Assembly Machinery (BAM) in Gram-negative bacteria; and the Sorting and Assembly [...] Read more.
β-barrel proteins are the highly abundant in the outer membranes of Gram-negative bacteria and the mitochondria in eukaryotes. The assembly of β-barrels is mediated by two evolutionary conserved machineries; the β-barrel Assembly Machinery (BAM) in Gram-negative bacteria; and the Sorting and Assembly Machinery (SAM) in mitochondria. Although the BAM and SAM have functionally conserved roles in the membrane integration and folding of β-barrel proteins, apart from the central BamA and Sam50 proteins, the remaining components of each of the complexes have diverged remarkably. For example all of the accessory components of the BAM complex characterized to date are located in the bacterial periplasm, on the same side as the N-terminal domain of BamA. This is the same side of the membrane as the substrates that are delivered to the BAM. On the other hand, all of the accessory components of the SAM complex are located on the cytosolic side of the membrane, the opposite side of the membrane to the N-terminus of Sam50 and the substrate receiving side of the membrane. Despite the accessory subunits being located on opposite sides of the membrane in each system, it is clear that each system is functionally equivalent with bacterial proteins having the ability to use the eukaryotic SAM and vice versa. In this review, we summarize the similarities and differences between the BAM and SAM complexes, highlighting the possible selecting pressures on bacteria and eukaryotes during evolution. It is also now emerging that bacterial pathogens utilize the SAM to target toxins and effector proteins to host mitochondria and this will also be discussed from an evolutionary perspective. Full article
(This article belongs to the Special Issue Membrane Transport)
Figures

Open AccessReview Biochemistry of Bacterial Multidrug Efflux Pumps
Int. J. Mol. Sci. 2012, 13(4), 4484-4495; doi:10.3390/ijms13044484
Received: 24 February 2012 / Revised: 9 March 2012 / Accepted: 15 March 2012 / Published: 10 April 2012
Cited by 17 | PDF Full-text (213 KB) | HTML Full-text | XML Full-text
Abstract
Bacterial pathogens that are multi-drug resistant compromise the effectiveness of treatment when they are the causative agents of infectious disease. These multi-drug resistance mechanisms allow bacteria to survive in the presence of clinically useful antimicrobial agents, thus reducing the efficacy of chemotherapy [...] Read more.
Bacterial pathogens that are multi-drug resistant compromise the effectiveness of treatment when they are the causative agents of infectious disease. These multi-drug resistance mechanisms allow bacteria to survive in the presence of clinically useful antimicrobial agents, thus reducing the efficacy of chemotherapy towards infectious disease. Importantly, active multi-drug efflux is a major mechanism for bacterial pathogen drug resistance. Therefore, because of their overwhelming presence in bacterial pathogens, these active multi-drug efflux mechanisms remain a major area of intense study, so that ultimately measures may be discovered to inhibit these active multi-drug efflux pumps. Full article
(This article belongs to the Special Issue Membrane Transport)
Open AccessReview The Intriguing Life of Autophagosomes
Int. J. Mol. Sci. 2012, 13(3), 3618-3635; doi:10.3390/ijms13033618
Received: 30 January 2012 / Revised: 2 March 2012 / Accepted: 7 March 2012 / Published: 19 March 2012
Cited by 9 | PDF Full-text (418 KB) | HTML Full-text | XML Full-text
Abstract
Autophagosomes are double-membrane vesicles characteristic of macroautophagy, a degradative pathway for cytoplasmic material and organelles terminating in the lysosomal or vacuole compartment for mammals and yeast, respectively. This highly dynamic, multi-step process requires significant membrane reorganization events at different stages of the [...] Read more.
Autophagosomes are double-membrane vesicles characteristic of macroautophagy, a degradative pathway for cytoplasmic material and organelles terminating in the lysosomal or vacuole compartment for mammals and yeast, respectively. This highly dynamic, multi-step process requires significant membrane reorganization events at different stages of the macroautophagic process. Such events include exchange and flow of lipids and proteins between membranes and vesicles (e.g., during initiation and growth of the phagophore), vesicular positioning and trafficking within the cell (e.g., autophagosome location and movement) and fusion of autophagosomes with the boundary membranes of the degradative compartment. Here, we review current knowledge on the contribution of different organelles to the formation of autophagosomes, their trafficking and fate within the cell. We will consider some of the unresolved questions related to the molecular mechanisms that regulate the “life and death” of the autophagosome. Full article
(This article belongs to the Special Issue Membrane Transport)
Open AccessReview Arsenic and Antimony Transporters in Eukaryotes
Int. J. Mol. Sci. 2012, 13(3), 3527-3548; doi:10.3390/ijms13033527
Received: 10 February 2012 / Revised: 29 February 2012 / Accepted: 7 March 2012 / Published: 15 March 2012
Cited by 21 | PDF Full-text (713 KB) | HTML Full-text | XML Full-text
Abstract
Arsenic and antimony are toxic metalloids, naturally present in the environment and all organisms have developed pathways for their detoxification. The most effective metalloid tolerance systems in eukaryotes include downregulation of metalloid uptake, efflux out of the cell, and complexation with phytochelatin [...] Read more.
Arsenic and antimony are toxic metalloids, naturally present in the environment and all organisms have developed pathways for their detoxification. The most effective metalloid tolerance systems in eukaryotes include downregulation of metalloid uptake, efflux out of the cell, and complexation with phytochelatin or glutathione followed by sequestration into the vacuole. Understanding of arsenic and antimony transport system is of high importance due to the increasing usage of arsenic-based drugs in the treatment of certain types of cancer and diseases caused by protozoan parasites as well as for the development of bio- and phytoremediation strategies for metalloid polluted areas. However, in contrast to prokaryotes, the knowledge about specific transporters of arsenic and antimony and the mechanisms of metalloid transport in eukaryotes has been very limited for a long time. Here, we review the recent advances in understanding of arsenic and antimony transport pathways in eukaryotes, including a dual role of aquaglyceroporins in uptake and efflux of metalloids, elucidation of arsenic transport mechanism by the yeast Acr3 transporter and its role in arsenic hyperaccumulation in ferns, identification of vacuolar transporters of arsenic-phytochelatin complexes in plants and forms of arsenic substrates recognized by mammalian ABC transporters. Full article
(This article belongs to the Special Issue Membrane Transport)

Other

Jump to: Research, Review

Open AccessOpinion The Kiss-and-Run Model of Intra-Golgi Transport
Int. J. Mol. Sci. 2012, 13(6), 6800-6819; doi:10.3390/ijms13066800
Received: 9 April 2012 / Revised: 9 May 2012 / Accepted: 22 May 2012 / Published: 5 June 2012
Cited by 10 | PDF Full-text (231 KB) | HTML Full-text | XML Full-text
Abstract
The Golgi apparatus (GA) is the main station along the secretory pathway. Mechanisms of intra-Golgi transport remain unresolved. Three models compete with each other for the right to be defined as the paradigm. The vesicular model cannot explain the following: (1) lipid [...] Read more.
The Golgi apparatus (GA) is the main station along the secretory pathway. Mechanisms of intra-Golgi transport remain unresolved. Three models compete with each other for the right to be defined as the paradigm. The vesicular model cannot explain the following: (1) lipid droplets and aggregates of procollagen that are larger than coatomer I (COPI)-dependent vesicles are transported across the GA; and (2) most anterograde cargoes are depleted in COPI vesicles. The compartment progression/maturation model has the following problems: (1) most Golgi-resident proteins are depleted in COPI vesicles; (2) there are no COPI vesicles for the recycling of the resident proteins in the trans-most-Golgi cisterna; and (3) different proteins have different rates of intra-Golgi transport. The diffusion model based on permanent inter-cisternal connections cannot explain the existence of lipid, ionic and protein gradients across the Golgi stacks. In contrast, the kiss-and-run model has the potential to explain most of the experimental observations. The kiss-and-run model can be symmetric when fusion and then fission occurs in the same place, and asymmetric when fusion takes place in one location, whereas fission takes place in another. The asymmetric kiss-and-run model resembles the carrier maturation mechanism, and it can be used to explain the transport of large cargo aggregates. Full article
(This article belongs to the Special Issue Membrane Transport)

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