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Human Trafficking

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181. Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors Full Text available with Trip Pro

Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated (...) polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors. The link between the TZ and upstream vesicle trafficking has been little explored to date. Moreover, the role of the small GTPase Rab8 in opsin-carrier vesicle (OCV) trafficking has been recently questioned in a mouse

2017 PLoS genetics

182. Antagonistic regulation of trafficking to Caenorhabditis elegans sensory cilia by a Retinal Degeneration 3 homolog and retromer Full Text available with Trip Pro

Antagonistic regulation of trafficking to Caenorhabditis elegans sensory cilia by a Retinal Degeneration 3 homolog and retromer Sensory neurons often possess cilia with elaborate membrane structures that are adapted to the sensory modality of the host cell. Mechanisms that target sensory transduction proteins to these specialized membrane domains remain poorly understood. Here, we show that a homolog of the human retinal dystrophy gene Retinal Degeneration 3 (RD3) is a Golgi-associated protein (...) required for efficient trafficking of a sensory receptor, the receptor-type guanylate cyclase GCY-9, to cilia in chemosensory neurons of the nematode Caenorhabditis elegans The trafficking defect caused by mutation of the nematode RD3 homolog is suppressed in vivo by mutation of key components of the retromer complex, which mediates recycling of cargo from endosomes to the Golgi. Our data show that there exists a critical balance in sensory neurons between the rates of anterograde and retrograde

2017 Proceedings of the National Academy of Sciences of the United States of America

183. Breast milk cells trafficking induces microchimerism-mediated immune system maturation in the infant. Full Text available with Trip Pro

Breast milk cells trafficking induces microchimerism-mediated immune system maturation in the infant. Initiating breastfeeding within the first hour of life confers an important benefit in terms of child mortality and severe morbidity. Intestinal permeability to ingested macromolecules and immunoglobulins is limited to the first days of human life. These exchanges cease in the very early post-partum period but may increase beyond the neonatal period in response to local inflammation (...) or introduction of a weaning food. From animal- and limited human-based observations, compelling evidence points out to breastmilk cells also trafficking from mother to infant mucosal tissues and participating to the maternal microchimerism. The precise nature of breastmilk cells that are involved is presently not known but likely includes progenitor/stem cells-representing up to 6% of breastmilk cells-with possible contribution of mature immune cells. Stem cell microchimerism may induce tolerance to non

2017 Pediatric Allergy and Immunology

184. Par3 and aPKC regulate BACE1 endosome-to-TGN trafficking through PACS1. Full Text available with Trip Pro

show that partitioning defective 3 (Par3) facilitates BACE1 retrograde trafficking from endosomes to the TGN. Par3 functions through aPKC-mediated phosphorylation of BACE1 on Ser498, which in turn promotes the interaction between BACE1 and phosphofurin acidic cluster sorting protein 1 and facilitates the retrograde trafficking of BACE1 to the TGN. In human AD brains, there is a significant decrease in Ser498 phosphorylation of BACE1 suggesting that defective phosphorylation-dependent retrograde (...) Par3 and aPKC regulate BACE1 endosome-to-TGN trafficking through PACS1. The cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE1) is the rate-limiting step in beta amyloid generation during Alzheimer's disease (AD) pathogenesis. In AD brains, BACE1 is abnormally accumulated in endocytic compartments, where the acidic pH is optimal for its activity. However, mechanisms regulating the endosome-to-trans-Golgi network (TGN) retrieval of BACE1 remain unclear. Here, we

2017 Neurobiology of Aging

185. Semaphorin4D drives CD8<sup>+</sup> T cell lesional trafficking in oral lichen planus via CXCL9/CXCL10 upregulations in oral keratinocytes. Full Text available with Trip Pro

. In this study, we sought to explicate the effect of Sema4D on human oral keratinocytes and its capacity to drive CD8+ T-cell lesional trafficking via chemokine modulation. We found that upregulations of sSema4D in OLP tissues and blood were positively correlated with disease severity and activity. In vitro observation revealed that Sema4D induced C-X-C motif chemokine ligand 9/C-X-C motif chemokine ligand 10 production by binding to plexin-B1 via protein kinase B-NF-κB cascade in human oral keratinocytes (...) Semaphorin4D drives CD8+ T cell lesional trafficking in oral lichen planus via CXCL9/CXCL10 upregulations in oral keratinocytes. Chemokine-mediated CD8+ T-cell recruitment is an essential but not well-established event for the persistence of oral lichen planus (OLP). Semaphorin 4D (Sema4D)/CD100 is implicated in immune dysfunction, chemokine modulation, and cell migration, which are critical aspects for OLP progression, but its implication in OLP pathogenesis has not been determined

2017 Journal of Investigative Dermatology

186. MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway. Full Text available with Trip Pro

MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway. The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human (...) embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein). MAS1R internalization was evaluated by measuring the MAS1R present in the plasma membrane after agonist stimulation using a ligand-binding assay. MAS1R trafficking was evaluated by its colocalization with trafficking markers. MAS1R internalization was blocked in the presence of shRNAcaveolin-1 and with dominant negatives for Eps15 (a protein involved in endocytosed Rs

2017 Hypertension

187. Labour trafficking: Challenges and opportunities from an occupational health perspective. Full Text available with Trip Pro

Labour trafficking: Challenges and opportunities from an occupational health perspective. In this essay for the collection on Human Trafficking, Exploitation, and Health, Elena Ronda-Perez and colleague discuss ways occupational health services can detect and address labour trafficking.

2017 PLoS medicine

188. A Targeted RNAi Screen Identifies Endocytic Trafficking Factors that Control GLP-1 Receptor Signaling in Pancreatic Beta Cells. Full Text available with Trip Pro

characterized in mouse and human β-cell lines and human islets. While HIP1 was required for the coupling of cell surface GLP-1R activation with clathrin-dependent endocytosis, the SNXs were found to control the balance between GLP-1R plasma membrane recycling and lysosomal degradation and, in doing so, determine the overall β-cell incretin responses. We thus identify key modulators of GLP-1R trafficking and signaling that might provide novel targets to enhance insulin secretion in T2D.© 2017 by the American (...) A Targeted RNAi Screen Identifies Endocytic Trafficking Factors that Control GLP-1 Receptor Signaling in Pancreatic Beta Cells. The glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) is a key target for type 2 diabetes (T2D) treatment. Because endocytic trafficking of agonist-bound receptors is one of the most important routes for regulation of receptor signaling, a better understanding of this process may facilitate the development of new T2D therapeutic strategies. Here, we screened 29

2017 Diabetes

189. The trafficking of women and girls in Taiwan: characteristics of victims, perpetrators, and forms of exploitation. Full Text available with Trip Pro

The trafficking of women and girls in Taiwan: characteristics of victims, perpetrators, and forms of exploitation. Prior to the passing of 2009 Human Trafficking Prevention Act (HTPA), human trafficking was underestimated in Taiwan. In the past, domestic trafficking in women and girls often targeted vulnerable groups such as young girls from poor families or minority groups. Since the 1990s, an increasing flow of immigrant women, mainly from Vietnam and Indonesia and some from China (...) , into Taiwan has created a new group of Human Trafficking victims. The current study intends to identify, describe, and categorize reported and prosecuted human trafficking cases involving women and girls according to the HTPA in Taiwan.Using the court proceedings of prosecuted trafficking in women and girls cases under Taiwan's HTPA from all 21 districts in Taiwan from 2009 to 2012 under the title keyword of 'Human Trafficking', this current study aims to categorize different patterns of existing

2017 BMC Women's Health

190. Identifying and Assisting Sexually Exploited and Trafficked Patients Seeking Women's Health Care Services. Full Text available with Trip Pro

Identifying and Assisting Sexually Exploited and Trafficked Patients Seeking Women's Health Care Services. It is estimated that 21 million people are trafficked worldwide, including 11.4 million women and girls. Approximately 4.5 million are forced to do sexual labor. The exact prevalence of human trafficking is difficult to ascertain, however, given the limitations of data collection in an illegal industry. Obstetrician-gynecologists should not only be aware of the widespread nature of human (...) trafficking, but also have the tools to assess patients for trafficking and respond to victim identifications. Patients may present with signs of physical abuse, depression, anxiety, posttraumatic stress disorder, substance use, sexually transmitted infections, pregnancy, and nonspecific somatic complaints. As with intimate partner violence, clinicians should be suspicious if the patient is accompanied by an individual who refuses to leave her side. Other potential red flags include patients with wounds

2017 Obstetrics and Gynecology

191. Harnessing membrane trafficking to promote cancer spreading and invasion: The case of RAB2A Full Text available with Trip Pro

that led to the identification of the small GTPase RAB2A, not previously involved in cancer dissemination, as pivotal for the acquisition of pericellular proteolysis, cell dissemination and distant metastatic spreading of human breast cancer. At the cellular levels, RAB2A controls both canonical polarized Golgi-to-Plasma membrane trafficking of the junctional protein E-cadherin, and post-endocytic trafficking of the membrane-bound metalloprotease, MT1-MMP. This finding reveals an unexpected plasticity (...) Harnessing membrane trafficking to promote cancer spreading and invasion: The case of RAB2A How cancer disseminates and metastasizes remains an outstanding open question. Emerging evidence indicates that membrane trafficking is frequently harnessed by tumors of epithelial origin to acquire a mesenchymal program of invasiveness. However, the critical molecular hubs used by cancer cells this context have only began to be elucidated. Here, we discussed the results of a recent phenotypic screening

2017 Small GTPases

192. Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: Intracellular delivery, trafficking and mechanisms of cell injury Full Text available with Trip Pro

Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: Intracellular delivery, trafficking and mechanisms of cell injury Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal (...) laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury. We demonstrate that O157 OMVs carry a cocktail of key virulence factors of EHEC O157 including Shiga toxin 2a (Stx2a), cytolethal distending toxin V (CdtV), EHEC hemolysin, and flagellin. The toxins are internalized by cells via dynamin-dependent endocytosis of OMVs

2017 PLoS pathogens

193. Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential for Endoplasmic Reticulum to Outer Mitochondrial Membrane Protein Transport Full Text available with Trip Pro

Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential for Endoplasmic Reticulum to Outer Mitochondrial Membrane Protein Transport Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known (...) as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM. By disruption of phosphofurin acidic cluster sorting protein 2 (PACS-2), mitofusins (Mfn1/2), and dynamin related protein 1 (Drp1), we find these conventional pathways for ER to the mitochondria trafficking are dispensable for vMIA

2017 Scientific reports

194. Fibronectin connecting segment-1 peptide inhibits pathogenic leukocyte trafficking and inflammatory demyelination in experimental models of chronic inflammatory demyelinating polyradiculoneuropathy Full Text available with Trip Pro

intraperitoneal injection with appropriate controls. Neurobehavioral measures of disease severity, motor nerve electrophysiology assessments and histopathological quantification of inflammation and morphometric assessment of demyelination were performed to determine in vivo efficacy. The biological relevance of FNCS1 and CD49d in CIDP was evaluated by immunohistochemical detection in affected patient sural nerve biopsies. 25μM FNCS1 peptide maximally inhibited CIDP leukocyte trafficking at the human BNB (...) Fibronectin connecting segment-1 peptide inhibits pathogenic leukocyte trafficking and inflammatory demyelination in experimental models of chronic inflammatory demyelinating polyradiculoneuropathy The molecular determinants of pathogenic leukocyte migration across the blood-nerve barrier (BNB) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are unknown. Specific disease modifying therapies for CIDP are also lacking. Fibronectin connecting segment-1 (FNCS1), an alternatively

2017 Experimental neurology

195. Expression and trafficking of placental microRNAs at the feto-maternal interface Full Text available with Trip Pro

Expression and trafficking of placental microRNAs at the feto-maternal interface During pregnancy, placental trophoblasts at the feto-maternal interface produce a broad repertoire of microRNA (miRNA) species. These species include miRNA from the primate-specific chromosome 19 miRNA cluster (C19MC), which is expressed nearly exclusively in the placenta. Trafficking of these miRNAs among the maternal, placental, and fetal compartments is unknown. To determine miRNA expression and trafficking (...) patterns during pregnancy, we sequenced miRNAs in triads of human placenta and of maternal and fetal blood and found large subject-to-subject variability, with C19MC exhibiting compartment-specific expression. We therefore created humanized mice that transgenically express the entire 160-kb human C19MC locus or lentivirally express C19MC miRNA members selectively in the placenta. C19MC transgenic mice expressed a low level of C19MC miRNAs in diverse organs. When pregnant, female C19MC mice exhibited

2017 The FASEB Journal

196. An Aberrant Phosphorylation of Amyloid Precursor Protein Tyrosine Regulates Its Trafficking and the Binding to the Clathrin Endocytic Complex in Neural Stem Cells of Alzheimer's Disease Patients Full Text available with Trip Pro

destinations inside neurons and identifying the mechanisms responsible for the generation of Aβ are thus the keys for the advancement of new therapies. We previously developed a mouse model with a mutation at tyrosine (Tyr) 682 in the C-terminus of APP. This residue is needed for APP to bind to the coating protein Clathrin and to the Clathrin adaptor protein AP2 as well as for the correct APP trafficking and sorting in neurons. By extending these findings to humans, we found that APP binding to Clathrin (...) An Aberrant Phosphorylation of Amyloid Precursor Protein Tyrosine Regulates Its Trafficking and the Binding to the Clathrin Endocytic Complex in Neural Stem Cells of Alzheimer's Disease Patients Alzheimer's disease (AD) is the most common cause of dementia and is likely caused by defective amyloid precursor protein (APP) trafficking and processing in neurons leading to amyloid plaques containing the amyloid-β (Aβ) APP peptide byproducts. Understanding how APP is targeted to selected

2017 Frontiers in molecular neuroscience

197. Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways Full Text available with Trip Pro

Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways Phosphoinositides are lipids involved in the vesicular transport of proteins and lipids between the different compartments of eukaryotic cells. They act by recruiting and/or activating effector proteins and thus are involved in regulating various cellular functions, such as vesicular budding, membrane fusion and cytoskeleton dynamics. Although detected in small concentrations in membranes, their role (...) is essential to cell function, since imbalance in their concentrations is a hallmark of many cancers. Their synthesis involves phosphorylating/dephosphorylating positions D3, D4 and/or D5 of their inositol ring by specific lipid kinases and phosphatases. This process is tightly regulated and specific to the different intracellular membranes. Most enzymes involved in phosphoinositide synthesis are conserved between yeast and human, and their loss of function leads to severe diseases (cancer, myopathy

2017 International journal of molecular sciences

198. Quality control and organelle trafficking: ensuring functional organelles and cells Full Text available with Trip Pro

Quality control and organelle trafficking: ensuring functional organelles and cells 28292912 2018 12 24 2018 12 24 1939-4586 28 6 2017 03 15 Molecular biology of the cell Mol. Biol. Cell Quality control and organelle trafficking: ensuring functional organelles and cells. 701-702 10.1091/mbc.E16-11-0798 Brill Julie A JA Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada julie.brill@sickkids.ca rutter@biochem.utah.edu. Rutter Jared J Department of Biochemistry (...) , University of Utah/Howard Hughes Medical Institute, Salt Lake City, UT 84112 julie.brill@sickkids.ca rutter@biochem.utah.edu. eng HHMI Howard Hughes Medical Institute United States Journal Article Research Support, Non-U.S. Gov't United States Mol Biol Cell 9201390 1059-1524 IM Animals Biological Transport Congresses as Topic Drosophila melanogaster metabolism Humans Organelles metabolism Quality Control 2017 3 16 6 0 2017 3 16 6 0 2018 12 26 6 0 ppublish 28292912 28/6/701 10.1091/mbc.E16-11-0798

2017 Molecular biology of the cell

199. Differential Disruption of Nucleocytoplasmic Trafficking Pathways by Rhinovirus 2A Proteases Full Text available with Trip Pro

Differential Disruption of Nucleocytoplasmic Trafficking Pathways by Rhinovirus 2A Proteases The RNA rhinoviruses (RV) encode 2A proteases (2Apro) that contribute essential polyprotein processing and host cell shutoff functions during infection, including the cleavage of Phe/Gly-containing nucleoporin proteins (Nups) within nuclear pore complexes (NPC). Within the 3 RV species, multiple divergent genotypes encode diverse 2Apro sequences that act differentially on specific Nups. Since only (...) subsets of Phe/Gly motifs, particularly those within Nup62, Nup98, and Nup153, are recognized by transport receptors (karyopherins) when trafficking large molecular cargos through the NPC, the processing preferences of individual 2Apro predict RV genotype-specific targeting of NPC pathways and cargos. To test this idea, transformed HeLa cell lines were created with fluorescent cargos (mCherry) for the importin α/β, transportin 1, and transportin 3 import pathways and the Crm1-mediated export pathway

2017 Journal of virology

200. Tpl2 promotes neutrophil trafficking, oxidative burst, and bacterial killing Full Text available with Trip Pro

Tpl2 promotes neutrophil trafficking, oxidative burst, and bacterial killing Tumor progression locus 2 (Tpl2) is a serine/threonine kinase that promotes inflammatory cytokine production by activating the MEK/ERK pathway. Tpl2 has been shown to be important for eliciting the inflammatory properties of macrophages; however, there is relatively little known about the contribution of Tpl2 to neutrophil effector functions. This is an important consideration, as neutrophils provide the first line (...) of defense against infection in the innate immune system. We found that Tpl2 is expressed in both human and murine neutrophils, suggesting a potential function for Tpl2 in this lineage. Despite significantly higher proportions of bone marrow (BM) neutrophils in Tpl2-deficient (Tpl2-/- ) mice compared with wild-type (WT) mice, Tpl2-/- mice have significantly reduced proportions of circulating neutrophils. Tpl2-/- neutrophils show impaired recruitment to thioglycollate, which was primarily a result

2017 Journal of leukocyte biology

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