Transport of Nucleoside Analogs Across the Plasma Membrane: A Clue to Understanding Drug-Induced Cytotoxicity

2009 ◽  
Vol 10 (4) ◽  
pp. 347-358 ◽  
Author(s):  
I. Huber-Ruano ◽  
M. Pastor-Anglada
Keyword(s):  
Plasma Membrane ◽  
Nucleoside Analogs ◽  
Drug Induced

Plasma membrane cytochromes P450 as neoantigens and autoimmune targets in drug-induced hepatitis

1997 ◽  
Vol 26 ◽  
pp. 23-30 ◽  
Author(s):  
Marie-Anne Robin ◽  
Marie Le Roy ◽  
Véronique Descatoire ◽  
Dominique Pessayre
Keyword(s):  
Plasma Membrane ◽  
Cytochromes P450 ◽  
Drug Induced

scholarly journals Birbeck Granules Are Subdomains of Endosomal Recycling Compartment in Human Epidermal Langerhans Cells, Which Form Where Langerin Accumulates

2002 ◽  
Vol 13 (1) ◽  
pp. 317-335 ◽  
Author(s):  
Ray Mc Dermott ◽  
Umit Ziylan ◽  
Danièle Spehner ◽  
Huguette Bausinger ◽  
Dan Lipsker ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Langerhans Cells ◽  
Birbeck Granule ◽  
Drug Induced ◽  
Intracellular Location ◽  
Birbeck Granules ◽  
Endosomal Recycling ◽  
Endosomal Membranes ◽  
And Function ◽  
Epidermal Langerhans Cells

Birbeck granules are unusual rod-shaped structures specific to epidermal Langerhans cells, whose origin and function remain undetermined. We investigated the intracellular location and fate of Langerin, a protein implicated in Birbeck granule biogenesis, in human epidermal Langerhans cells. In the steady state, Langerin is predominantly found in the endosomal recycling compartment and in Birbeck granules. Langerin internalizes by classical receptor-mediated endocytosis and the first Birbeck granules accessible to endocytosed Langerin are those connected to recycling endosomes in the pericentriolar area, where Langerin accumulates. Drug-induced inhibition of endocytosis results in the appearance of abundant open-ended Birbeck granule-like structures appended to the plasma membrane, whereas inhibition of recycling induces Birbeck granules to merge with a tubular endosomal network. In mature Langerhans cells, Langerin traffic is abolished and the loss of internal Langerin is associated with a concomitant depletion of Birbeck granules. Our results demonstrate an exchange of Langerin between early endosomal compartments and the plasma membrane, with dynamic retention in the endosomal recycling compartment. They show that Birbeck granules are not endocytotic structures, rather they are subdomains of the endosomal recycling compartment that form where Langerin accumulates. Finally, our results implicate ADP-ribosylation factor proteins in Langerin trafficking and the exchange between Birbeck granules and other endosomal membranes.

Translocation of Nucleoside Analogs Across the Plasma Membrane in Hematologic Malignancies

2011 ◽  
Vol 30 (12) ◽  
pp. 1324-1340 ◽  
Author(s):  
Paula X. Fernández-Calotti ◽  
Dolors Colomer ◽  
Marçal Pastor-Anglada
Keyword(s):  
Plasma Membrane ◽  
Nucleoside Analogs ◽  
Hematologic Malignancies

scholarly journals Translocatable voltage-gated Ca2+ channel β subunits in α1–β complexes reveal competitive replacement yet no spontaneous dissociation

2018 ◽  
Vol 115 (42) ◽  
pp. E9934-E9943 ◽  
Author(s):  
Jun-Hee Yeon ◽  
Cheon-Gyu Park ◽  
Bertil Hille ◽  
Byung-Chang Suh
Keyword(s):  
Plasma Membrane ◽  
Channel Gating ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Intracellular Loop ◽  
Drug Induced ◽  
Interaction Domain ◽  
Intact Cells ◽  
Voltage Gated ◽  
The Stability

β subunits of high voltage-gated Ca2+ (CaV) channels promote cell-surface expression of pore-forming α1 subunits and regulate channel gating through binding to the α-interaction domain (AID) in the first intracellular loop. We addressed the stability of CaV α1B–β interactions by rapamycin-translocatable CaV β subunits that allow drug-induced sequestration and uncoupling of the β subunit from CaV2.2 channel complexes in intact cells. Without CaV α1B/α2δ1, all modified β subunits, except membrane-tethered β2a and β2e, are in the cytosol and rapidly translocate upon rapamycin addition to anchors on target organelles: plasma membrane, mitochondria, or endoplasmic reticulum. In cells coexpressing CaV α1B/α2δ1 subunits, the translocatable β subunits colocalize at the plasma membrane with α1B and stay there after rapamycin application, indicating that interactions between α1B and bound β subunits are very stable. However, the interaction becomes dynamic when other competing β isoforms are coexpressed. Addition of rapamycin, then, switches channel gating and regulation by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] lipid. Thus, expression of free β isoforms around the channel reveals a dynamic aspect to the α1B–β interaction. On the other hand, translocatable β subunits with AID-binding site mutations are easily dissociated from CaV α1B on the addition of rapamycin, decreasing current amplitude and PI(4,5)P2 sensitivity. Furthermore, the mutations slow CaV2.2 current inactivation and shift the voltage dependence of activation to more positive potentials. Mutated translocatable β subunits work similarly in CaV2.3 channels. In sum, the strong interaction of CaV α1B–β subunits can be overcome by other free β isoforms, permitting dynamic changes in channel properties in intact cells.

scholarly journals Ubiquitination-dependent quality control of hERG K+ channel with acquired and inherited conformational defect at the plasma membrane

2013 ◽  
Vol 24 (24) ◽  
pp. 3787-3804 ◽  
Author(s):  
Pirjo M. Apaja ◽  
Brian Foo ◽  
Tsukasa Okiyoneda ◽  
William C. Valinsky ◽  
Herve Barriere ◽  
...  
Keyword(s):  
Quality Control ◽  
Plasma Membrane ◽  
Membrane Trafficking ◽  
Critical Role ◽  
Sudden Cardiac Arrest ◽  
K Channel ◽  
Missense Mutations ◽  
Drug Induced ◽  
Interacting Protein ◽  
Expression Phenotype

Membrane trafficking in concert with the peripheral quality control machinery plays a critical role in preserving plasma membrane (PM) protein homeostasis. Unfortunately, the peripheral quality control may also dispose of partially or transiently unfolded polypeptides and thereby contribute to the loss-of-expression phenotype of conformational diseases. Defective functional PM expression of the human ether-a-go-go–related gene (hERG) K+ channel leads to the prolongation of the ventricular action potential that causes long QT syndrome 2 (LQT2), with increased propensity for arrhythmia and sudden cardiac arrest. LQT2 syndrome is attributed to channel biosynthetic processing defects due to mutation, drug-induced misfolding, or direct channel blockade. Here we provide evidence that a peripheral quality control mechanism can contribute to development of the LQT2 syndrome. We show that PM hERG structural and metabolic stability is compromised by the reduction of extracellular or intracellular K+ concentration. Cardiac glycoside–induced intracellular K+ depletion conformationally impairs the complex-glycosylated channel, which provokes chaperone- and C-terminal Hsp70-interacting protein–dependent polyubiquitination, accelerated internalization, and endosomal sorting complex required for transport–dependent lysosomal degradation. A similar mechanism contributes to the down-regulation of PM hERG harboring LQT2 missense mutations, with incomplete secretion defect. These results suggest that PM quality control plays a determining role in the loss-of-expression phenotype of hERG in certain hereditary and acquired LTQ2 syndromes.

Drug-induced changes in the plasma membrane of Microsporum canis.

1977 ◽  
Vol 96 (5) ◽  
pp. 515-520 ◽  
Author(s):  
V. PUCCINELLI ◽  
M. INNOCENTI ◽  
A. LASAGNI ◽  
R. CAPUTO
Keyword(s):  
Plasma Membrane ◽  
Microsporum Canis ◽  
Drug Induced ◽  
Induced Changes

A Surface Biotinylation Strategy for Reproducible Plasma Membrane Protein Purification and Tracking of Genetic and Drug-Induced Alterations

2016 ◽  
Vol 15 (2) ◽  
pp. 647-658 ◽  
Author(s):  
Katrin Hörmann ◽  
Alexey Stukalov ◽  
André C. Müller ◽  
Leonhard X. Heinz ◽  
Giulio Superti-Furga ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Protein ◽  
Protein Purification ◽  
Plasma Membrane Protein ◽  
Drug Induced

scholarly journals Single-site sonoporation disrupts actin cytoskeleton organization

2014 ◽  
Vol 11 (95) ◽  
pp. 20140071 ◽  
Author(s):  
Xian Chen ◽  
Ruen Shan Leow ◽  
Yaxin Hu ◽  
Jennifer M. F. Wan ◽  
Alfred C. H. Yu
Keyword(s):  
Plasma Membrane ◽  
Actin Cytoskeleton ◽  
Bubble Diameter ◽  
Single Site ◽  
Drug Induced ◽  
Cytoskeleton Organization ◽  
Ultrasound Frequency ◽  
Actin Cytoskeleton Organization ◽  
Cytoplasmic Accumulation ◽  
Confocal Fluorescence Imaging

Sonoporation is based upon an ultrasound–microbubble cavitation routine that physically punctures the plasma membrane on a transient basis. During such a process, the actin cytoskeleton may be disrupted in tandem because this network of subcellular filaments is physically interconnected with the plasma membrane. Here, by performing confocal fluorescence imaging of single-site sonoporation episodes induced by ultrasound-triggered collapse of a single targeted microbubble, we directly observed immediate rupturing of filamentary actin (F-actin) at the sonoporation site (cell type: ZR-75-30; ultrasound frequency: 1 MHz; peak negative pressure: 0.45 MPa; pulse duration: 30 cycles; bubble diameter: 2–4 µm). Also, through conducting a structure tensor analysis, we observed further disassembly of the F-actin network over the next 60 min after the onset of sonoporation. The extent of F-actin disruption was found to be more substantial in cells with higher uptake of sonoporation tracer. Commensurate with this process, cytoplasmic accumulation of globular actin (G-actin) was evident in sonoporated cells, and in turn the G-actin : F-actin ratio was increased in a trend similar to drug-induced (cytochalasin D) actin depolymerization. These results demonstrate that sonoporation is not solely a membrane-level phenomenon: organization of the actin cytoskeleton is concomitantly perturbed.

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