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Human Trafficking

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3281. Visualizing odorant receptor trafficking in living cells down to the single-molecule level Full Text available with Trip Pro

Visualizing odorant receptor trafficking in living cells down to the single-molecule level Despite the importance of trafficking for regulating G protein-coupled receptor signaling, for many members of the seven transmembrane helix protein family, such as odorant receptors, little is known about this process in live cells. Here, the complete life cycle of the human odorant receptor OR17-40 was directly monitored in living cells by ensemble and single-molecule imaging, using a double-labeling (...) strategy. While the overall, intracellular trafficking of the receptor was visualized continuously by using a GFP tag, selective imaging of cell surface receptors was achieved by pulse-labeling an acyl carrier protein tag. We found that OR17-40 efficiently translocated to the plasma membrane only at low expression, whereas at higher biosynthesis the receptor accumulated in intracellular compartments. Receptors in the plasma membrane showed high turnover resulting from constitutive internalization along

2006 Proceedings of the National Academy of Sciences of the United States of America

3282. Nucleolar trafficking is essential for nuclear export of intronless herpesvirus mRNA Full Text available with Trip Pro

Nucleolar trafficking is essential for nuclear export of intronless herpesvirus mRNA The nucleolus is the largest subnuclear structure and is plurifunctional in nature. Here, we demonstrate that nucleolar localization of a key herpesvirus regulatory protein is essential for its role in virus mRNA nuclear export. The herpesvirus saimiri ORF57 protein is a nucleocytoplasmic shuttle protein that is conserved in all herpesviruses and orchestrates the nuclear export of viral intronless mRNAs. We (...) demonstrate that expression of the ORF57 protein induces nucleolar redistribution of human TREX (transcription/export) proteins that are involved in mRNA nuclear export. Moreover, we describe a previously unidentified nucleolar localization signal within ORF57 that is composed of two distinct nuclear localization signals. Intriguingly, point mutations that ablate ORF57 nucleolar localization lead to a failure of ORF57-mediated viral mRNA nuclear export. Furthermore, nucleolar retargeting of the ORF57

2006 Proceedings of the National Academy of Sciences of the United States of America

3283. Protein Trafficking to the Apicoplast: Deciphering the Apicomplexan Solution to Secondary Endosymbiosis Full Text available with Trip Pro

Protein Trafficking to the Apicoplast: Deciphering the Apicomplexan Solution to Secondary Endosymbiosis 17513565 2007 10 23 2018 11 13 1535-9778 6 7 2007 Jul Eukaryotic cell Eukaryotic Cell Protein trafficking to the apicoplast: deciphering the apicomplexan solution to secondary endosymbiosis. 1081-8 Parsons Marilyn M Seattle Biomedical Research Institute, 307 Westlake Ave. North, Seattle, WA 98109, USA. marilyn.parsons@sbri.org Karnataki Anuradha A Feagin Jean E JE DeRocher Amy A eng R01 (...) AI050506 AI NIAID NIH HHS United States R01 AI050506-05 AI NIAID NIH HHS United States R01 AI50506 AI NIAID NIH HHS United States Journal Article Research Support, N.I.H., Extramural Review 2007 05 18 United States Eukaryot Cell 101130731 1535-9786 0 Membrane Proteins 0 Protozoan Proteins IM Animals Apicomplexa cytology physiology Humans Membrane Proteins metabolism Organelles metabolism ultrastructure Protein Transport physiology Protozoan Infections Protozoan Proteins metabolism Symbiosis 95 2007 5

2007 Eukaryotic cell

3284. Transmigration at the borders: Recycling and trafficking of adhesion molecules Full Text available with Trip Pro

Transmigration at the borders: Recycling and trafficking of adhesion molecules 19262105 2009 05 01 2018 11 13 1933-6926 2 2 2008 Apr-May Cell adhesion & migration Cell Adh Migr Transmigration at the borders: Recycling and trafficking of adhesion molecules. 55-6 Bonecchi Raffaella R Istituto Clinico Humanitas IRCCS, Rozzano, Italy. raffaella.bonecchi@humanitas.it eng Journal Article 2008 04 18 United States Cell Adh Migr 101469464 1933-6918 0 Cell Adhesion Molecules IM Cell Adhesion Molecules (...) metabolism Cell Movement Endothelial Cells cytology metabolism Humans Protein Transport 2009 3 6 9 0 2009 3 6 9 0 2009 5 2 9 0 ppublish 19262105 6459 PMC2634983 Traffic. 2001 Mar;2(3):149-59 11260520 Nature. 2003 Feb 13;421(6924):748-53 12610627 Blood. 2008 Aug 1;112(3):493-503 18480427 Immunol Rev. 2007 Aug;218:178-96 17624953 J Exp Med. 2008 Apr 14;205(4):951-66 18378793 Blood. 2006 Oct 15;108(8):2624-31 16638931

2008 Cell adhesion & migration

3285. c-Src trafficking and co-localization with the EGF Receptor promotes EGF ligand-independent EGF Receptor Activation and Signaling Full Text available with Trip Pro

c-Src trafficking and co-localization with the EGF Receptor promotes EGF ligand-independent EGF Receptor Activation and Signaling c-Src is a non-receptor tyrosine kinase that associates with both the plasma membrane and endosomal compartments. In many human cancers, especially breast cancer, c-Src and the EGF receptor (EGFR) are overexpressed. Dual overexpression of c-Src and EGFR correlates with a Src-dependent increase in activation of EGFR, and synergism between these two tyrosine kinases (...) increases the mitogenic activity of EGFR. Despite extensive studies of the functional interaction between c-Src and EGFR, little is known about the interactions in the trafficking pathways for the two proteins and how that influences signaling. Given the synergism between c-Src and EGFR, and the finding that EGFR is internalized and can signal from endosomes, we hypothesized that c-Src and EGFR traffic together through the endocytic pathway. Here we use a regulatable c-SrcGFP fusion protein

2008 Cellular signalling

3286. Endocytic Trafficking of Sphingomyelin Depends on Its Acyl Chain Length Full Text available with Trip Pro

Endocytic Trafficking of Sphingomyelin Depends on Its Acyl Chain Length To study the principles of endocytic lipid trafficking, we introduced pyrene sphingomyelins (PyrSMs) with varying acyl chain lengths and domain partitioning properties into human fibroblasts or HeLa cells. We found that a long-chain, ordered-domain preferring PyrSM was targeted Hrs and Tsg101 dependently to late endosomal compartments and recycled to the plasma membrane in an NPC1- and cholesterol-dependent manner. A short (...) -chain, disordered domain preferring PyrSM recycled more effectively, by using Hrs-, Tsg101- and NPC1-independent routing that was insensitive to cholesterol loading. Similar chain length-dependent recycling was observed for unlabeled sphingomyelins (SMs). The findings 1) establish acyl chain length as an important determinant in the endocytic trafficking of SMs, 2) implicate ESCRT complex proteins and NPC1 in the endocytic recycling of ordered domain lipids to the plasma membrane, and 3) introduce

2007 Molecular biology of the cell

3287. A Novel Role for PA28γ-Proteasome in Nuclear Speckle Organization and SR Protein Trafficking Full Text available with Trip Pro

A Novel Role for PA28γ-Proteasome in Nuclear Speckle Organization and SR Protein Trafficking In eukaryotic cells, proteasomes play an essential role in intracellular proteolysis and are involved in the control of most biological processes through regulated degradation of key proteins. Analysis of 20S proteasome localization in human cell lines, using ectopic expression of its CFP-tagged alpha7 subunit, revealed the presence in nuclear foci of a specific and proteolytically active complex made (...) an alteration of intranuclear trafficking of SR proteins. Thus, our data identify proteasome-PA28gamma complexes as a novel regulator of NS organization and function, acting most likely through selective proteolysis. These results constitute the first demonstration of a role of a specific proteasome complex in a defined subnuclear compartment and suggest that proteolysis plays important functions in the precise control of splicing factors trafficking within the nucleus.

2008 Molecular biology of the cell

3288. Copper stimulates trafficking of a distinct pool of the Menkes copper ATPase (ATP7A) to the plasma membrane and diverts it into a rapid recycling pool. Full Text available with Trip Pro

Copper stimulates trafficking of a distinct pool of the Menkes copper ATPase (ATP7A) to the plasma membrane and diverts it into a rapid recycling pool. MNK (Menkes copper-translocating P-type ATPase, or the Menkes protein; ATP7A) plays a key role in regulating copper homoeostasis in humans. MNK has been shown to have a dual role in the cell: it delivers copper to cuproenzymes in the Golgi compartment and effluxes excess copper from the cell. These roles can be achieved through copper-regulated (...) trafficking of MNK. It has previously been shown to undergo trafficking from the trans -Golgi network to the plasma membrane in response to elevated copper concentrations, and to be endocytosed from the plasma membrane to the trans -Golgi network upon the removal of elevated copper. However, the fundamental question as to whether copper influences trafficking of MNK to or from the plasma membrane remained unanswered. In this study we utilized various methods of cell-surface biotinylation to attempt

2004 Biochemical Journal

3289. Benzoic Acid, a Weak Organic Acid Food Preservative, Exerts Specific Effects on Intracellular Membrane Trafficking Pathways in Saccharomyces cerevisiae Full Text available with Trip Pro

Benzoic Acid, a Weak Organic Acid Food Preservative, Exerts Specific Effects on Intracellular Membrane Trafficking Pathways in Saccharomyces cerevisiae Microbial spoilage of food causes losses of up to 40% of all food grown for human consumption worldwide. Yeast growth is a major factor in the spoilage of foods and beverages that are characterized by a high sugar content, low pH, and low water activity, and it is a significant economic problem. While growth of spoilage yeasts (...) analyses of the effects of benzoic acid on intracellular membrane trafficking revealed that there was specific inhibition of macroautophagy. The data suggest that the synergism between nitrogen starvation and benzoic acid is the result of inhibition of macroautophagy by benzoic acid and that a mechanistic understanding of this inhibition should be beneficial in the development of novel food preservation technologies.

2004 Applied and environmental microbiology

3290. LEDGF/p75 Determines Cellular Trafficking of Diverse Lentiviral but Not Murine Oncoretroviral Integrase Proteins and Is a Component of Functional Lentiviral Preintegration Complexes Full Text available with Trip Pro

LEDGF/p75 Determines Cellular Trafficking of Diverse Lentiviral but Not Murine Oncoretroviral Integrase Proteins and Is a Component of Functional Lentiviral Preintegration Complexes Human immunodeficiency virus type 1 (HIV-1), feline immunodeficiency virus (FIV), and Moloney murine leukemia virus (MoMLV) integrases were stably expressed to determine their intracellular trafficking. Each lentiviral integrase localized to cell nuclei in close association with chromatin while the murine (...) oncoretroviral integrase was cytoplasmic. Fusions of pyruvate kinase to the lentiviral integrases did not reveal transferable nuclear localization signals. The intracellular trafficking of each was determined instead by the transcriptional coactivator LEDGF/p75, which was required for nuclear localization. Stable small interfering RNA expression eliminated detectable LEDGF/p75 expression and caused dramatic, stable redistribution of each lentiviral integrase from nucleus to cytoplasm while the distribution

2004 Journal of virology

3291. Ion Trafficking through T-type Ca2+ Channels: A Way to Look at Channel Gating Position Full Text available with Trip Pro

Ion Trafficking through T-type Ca2+ Channels: A Way to Look at Channel Gating Position 15572340 2005 06 13 2018 11 13 0022-1295 124 6 2004 Dec The Journal of general physiology J. Gen. Physiol. Ion trafficking through T-type Ca2+ channels: a way to look at channel gating position. 619-22 Carbone Emilio E Department of Neuroscience, INFM Research Unit, University of Turin, Corso Raffaello 30, I-10125 Turin, Italy. emilio.carbone@unito.it eng Journal Article United States J Gen Physiol 2985110R (...) 0022-1295 0 Calcium Channels, T-Type SY7Q814VUP Calcium IM Animals Calcium metabolism Calcium Channels, T-Type physiology Calcium Signaling physiology Cell Membrane physiology Cell Membrane Permeability physiology Humans Ion Channel Gating physiology Ion Transport physiology Membrane Potentials physiology 2004 12 2 9 0 2005 6 14 9 0 2004 12 2 9 0 ppublish 15572340 jgp.200409199 10.1085/jgp.200409199 PMC2234028 Nature. 1984 May 31-Jun 6;309(5967):453-6 6328315 J Membr Biol. 2002 Jun 1;187(3):225-38

2004 The Journal of general physiology

3292. Crystal structure of subunit VPS25 of the endosomal trafficking complex ESCRT-II Full Text available with Trip Pro

Crystal structure of subunit VPS25 of the endosomal trafficking complex ESCRT-II Down-regulation of plasma membrane receptors via the endocytic pathway involves their monoubiquitylation, transport to endosomal membranes and eventual sorting into multi vesicular bodies (MVB) destined for lysosomal degradation. Successive assemblies of Endosomal Sorting Complexes Required for Transport (ESCRT-I, -II and III) largely mediate sorting of plasma membrane receptors at endosomal membranes (...) , the formation of multivesicular bodies and their release into the endosomal lumen. In addition, the human ESCRT-II has been shown to form a complex with RNA polymerase II elongation factor ELL in order to exert transcriptional control activity.Here we report the crystal structure of Vps25 at 3.1 A resolution. Vps25 crystallizes in a dimeric form and each monomer is composed of two winged helix domains arranged in tandem. Structural comparisons detect no conformational changes between unliganded Vps25

2004 BMC structural biology

3293. Pathogen effector protein screening in yeast identifies Legionella factors that interfere with membrane trafficking Full Text available with Trip Pro

Pathogen effector protein screening in yeast identifies Legionella factors that interfere with membrane trafficking Legionella pneumophila invades and replicates intracellularly in human and protozoan hosts. The bacteria use the Icm/Dot type IVB secretion system to translocate effectors that inhibit phagosome maturation and modulate host vesicle trafficking pathways. To understand how L. pneumophila modulates organelle trafficking in host cells, we carried out pathogen effector protein (...) screening in yeast, identifying L. pneumophila genes that produced membrane trafficking [vacuole protein sorting (VPS)] defects in yeast. We identified four L. pneumophila DNA fragments that perturb sorting of vacuolar proteins. Three encode ORFs of unknown function that are translocated via the Icm/Dot transporter from Legionella into macrophages. VPS inhibitor protein (Vip) A is a coiled-coil protein, VipD is a patatin domain-containing protein, and VipF contains an acetyltransferase domain

2005 Proceedings of the National Academy of Sciences of the United States of America

3294. Viral trafficking violations in axons: The herpesvirus case Full Text available with Trip Pro

Viral trafficking violations in axons: The herpesvirus case 15827114 2005 07 06 2018 11 13 0027-8424 102 16 2005 Apr 19 Proceedings of the National Academy of Sciences of the United States of America Proc. Natl. Acad. Sci. U.S.A. Viral trafficking violations in axons: the herpesvirus case. 5639-40 Greber Urs F UF Institute of Zoology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. ufgreber@zool.unizh.ch eng Comment Journal Article 2005 04 12 United States Proc Natl (...) Acad Sci U S A 7505876 0027-8424 0 Recombinant Fusion Proteins 0 Viral Proteins IM Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5832-7 15795370 Animals Axons metabolism Biological Transport physiology Ganglia, Spinal cytology Herpesvirus 1, Suid genetics metabolism Humans Recombinant Fusion Proteins genetics metabolism Viral Proteins metabolism 2005 4 14 9 0 2005 7 7 9 0 2005 4 14 9 0 ppublish 15827114 0501696102 10.1073/pnas.0501696102 PMC556310 EMBO J. 2001 Mar 15;20(6):1310-9 11250897 J Virol

2005 Proceedings of the National Academy of Sciences of the United States of America

3295. Gating and trafficking of ClC-2 chloride channel without cystathionine β-synthase domains Full Text available with Trip Pro

Gating and trafficking of ClC-2 chloride channel without cystathionine β-synthase domains 19011132 2009 02 04 2018 11 13 1469-7793 586 22 2008 Nov 15 The Journal of physiology J. Physiol. (Lond.) Gating and trafficking of ClC-2 chloride channel without cystathionine beta-synthase domains. 5289 10.1113/jphysiol.2008.164103 Arreola Jorge J Physics Institute, Universidad Autónoma de San Luís Potosí, Ave. Dr M Nava 6, San Luís Potosí, SLP, México, 78290. arreola@dec1.ifisica.uaslp.mx De Santiago (...) -Castillo José A JA Sánchez Jorge E JE Nieto Pablo G PG eng Comment Journal Article England J Physiol 0266262 0022-3751 0 Chloride Channels 0 ClC-2 chloride channels 0 Recombinant Proteins EC 4.2.1.22 Cystathionine beta-Synthase IM J Physiol. 2008 Nov 15;586(22):5325-36 18801843 Binding Sites Chloride Channels chemistry genetics metabolism Cystathionine beta-Synthase chemistry Humans In Vitro Techniques Ion Channel Gating Protein Structure, Tertiary Recombinant Proteins chemistry genetics metabolism

2008 The Journal of physiology

3296. Trafficking defects of the Southeast Asian ovalocytosis deletion mutant of anion exchanger 1 membrane proteins Full Text available with Trip Pro

Trafficking defects of the Southeast Asian ovalocytosis deletion mutant of anion exchanger 1 membrane proteins Human AE1 (anion exchanger 1) is a membrane glycoprotein found in erythrocytes and as a truncated form (kAE1) in the BLM (basolateral membrane) of a-intercalated cells of the distal nephron, where they carry out electroneutral chloride/bicarbonate exchange. SAO (Southeast Asian ovalocytosis) is a dominant inherited haematological condition arising from deletion of Ala400-Ala408 in AE1 (...) , resulting in a misfolded and transport-inactive protein present in the ovalocyte membrane. Heterozygotes with SAO are able to acidify their urine, without symptoms of dRTA (distal renal tubular acidosis) that can be associated with mutations in kAE1. We examined the effect of the SAO deletion on stability and trafficking of AE1 and kAE1 in transfected HEK-293 (human embryonic kidney) cells and kAE1 in MDCK (Madin-Darby canine kidney) epithelial cells. In HEK-293 cells, expression levels and stabilities

2005 Biochemical Journal

3297. Sequential Actions of Myotubularin Lipid Phosphatases Regulate Endosomal PI(3)P and Growth Factor Receptor Trafficking Full Text available with Trip Pro

Sequential Actions of Myotubularin Lipid Phosphatases Regulate Endosomal PI(3)P and Growth Factor Receptor Trafficking Two different human diseases, X-linked myotubular myopathy and Charcot-Marie-Tooth disease, result from mutant MTM1 or MTMR2 lipid phosphatases. Although events involved in endosomal PI(3)P and PI(3,5)P(2) synthesis are well established and pivotal in receptor signaling and degradation, enzymes involved in phosphoinositide degradation and their roles in trafficking (...) providing a molecular rationale for related human myo- and neuropathies.

2008 Molecular biology of the cell

3298. Rab proteins and Rab-associated proteins: major actors in the mechanism of protein-trafficking disorders Full Text available with Trip Pro

Rab proteins and Rab-associated proteins: major actors in the mechanism of protein-trafficking disorders Ras-associated binding (Rab) proteins and Rab-associated proteins are key regulators of vesicle transport, which is essential for the delivery of proteins to specific intracellular locations. More than 60 human Rab proteins have been identified, and their function has been shown to depend on their interaction with different Rab-associated proteins regulating Rab activation, post (...) -translational modification and intracellular localization. The number of known inherited disorders of vesicle trafficking due to Rab cycle defects has increased substantially during the past decade. This review describes the important role played by Rab proteins in a number of rare monogenic diseases as well as common multifactorial human ones. Although the clinical phenotype in these monogenic inherited diseases is highly variable and dependent on the type of tissue in which the defective Rab or its

2008 European journal of pediatrics

3299. Elevated CXCL12 expression in the bone marrow of NOD mice is associated with altered T cell and stem cell trafficking and diabetes development Full Text available with Trip Pro

Elevated CXCL12 expression in the bone marrow of NOD mice is associated with altered T cell and stem cell trafficking and diabetes development Type I diabetes (TID) is an autoimmune disease resulting from destruction of the insulin-producing beta-cells by autoreactive T cells. Studies have shown that polymorphisms of chemokine CXCL12 gene are linked to TID in humans. In non-obese diabetic (NOD) mice, which are predisposed to develop the disease, reduction of CXCL12 level leads to significant (...) , mobilizes T cells and HSC from the bone marrow to the periphery, concomitantly inhibits insulitis and delays the onset of diabetes.These results suggest that the elevated CXCL12 expression promotes TID in NOD mice by altering T cell and hematopoietic stem cell trafficking. The findings highlight the potential usefulness of AMD3100 to treat or prevent TID in humans.

2008 BMC immunology

3300. Internalization and trafficking of guanylyl (guanylate) cyclase/natriuretic peptide receptor A is regulated by an acidic tyrosine-based cytoplasmic motif GDAY Full Text available with Trip Pro

Internalization and trafficking of guanylyl (guanylate) cyclase/natriuretic peptide receptor A is regulated by an acidic tyrosine-based cytoplasmic motif GDAY We have identified a GDAY motif in the C-terminal domain of guanylyl cyclase (guanylate cyclase)/NPRA (natriuretic peptide receptor A) sequence, which serves a dual role as an internalization signal and a recycling signal. To delineate the role of the GDAY motif in receptor internalization and sequestration, we mutated Gly920, Asp921 (...) and Tyr923 to alanine residues (GDAY/AAAA) in the NPRA cDNA sequence. The cDNAs encoding wild-type and mutant receptors were transfected in HEK-293 cells (human embryonic kidney 293 cells). The internalization studies of ligand-receptor complexes revealed that endocytosis of 125I-ANP by HEK-293 cells expressing G920A, Y923A or GDAY/AAAA mutant receptor was decreased by almost 50% (P<0.001) when compared with cells expressing the wild-type receptor. However, the effect of D921A mutation on receptor

2005 Biochemical Journal

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