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https://www.readbyqxmd.com/read/29326436/p66shc-deficiency-enhances-cxcr4-and-ccr7-recycling-in-cll-b-cells-by-facilitating-their-dephosphorylation-dependent-release-from-%C3%AE-arrestin-at-early-endosomes
#1
Laura Patrussi, Nagaja Capitani, Francesca Cattaneo, Noemi Manganaro, Alessandra Gamberucci, Federica Frezzato, Veronica Martini, Andrea Visentin, Pier Giuseppe Pelicci, Mario M D'Elios, Livio Trentin, Gianpietro Semenzato, Cosima T Baldari
Neoplastic cell traffic abnormalities are central to the pathogenesis of chronic lymphocytic leukemia (CLL). Enhanced CXC chemokine receptor-4 (CXCR4) and chemokine receptor-7 (CCR7) recycling contributes to the elevated surface levels of these receptors on CLL cells. Here we have addressed the role of p66Shc, a member of the Shc family of protein adaptors the expression of which is defective in CLL cells, in CXCR4/CCR7 recycling. p66Shc reconstitution in CLL cells reduced CXCR4/CCR7 recycling, lowering their surface levels and attenuating B-cell chemotaxis, due to their accumulation in Rab5+ endosomes as serine-phosphoproteins bound to β-arrestin...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29322087/the-endosomal-protein-endotubin-is-required-for-enterocyte%C3%A2-differentiation
#2
Christopher M Cox, Ruifeng Lu, Kaan Salcin, Jean M Wilson
Background & Aims: During late embryonic development and through weaning, enterocytes of the ileum are highly endocytic. Defects in endocytosis and trafficking are implicated in neonatal disease, however, the mechanisms regulating trafficking during the developmental period are incompletely understood. The apical endosomal protein endotubin (EDTB) is highly expressed in the late embryonic and neonatal ileum. In epithelial cells in vitro, EDTB regulates both trafficking of tight junction proteins and proliferation through modulation of YAP activity...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29317286/the-a-enth-domain-containing-protein-ateca4-is-an-adaptor-protein-involved-in-cargo-recycling-from-the-trans-golgi-network-early-endosome-to-the-plasma-membrane
#3
Hong Hanh Nguyen, Myoung Hui Lee, Kyungyoung Song, Gyeongik Ahn, Jihyeong Lee, Inhwan Hwang
Endocytosis and subsequent trafficking pathways are crucial for regulating the activity of plasma membrane-localized proteins. Depending on cellular and physiological conditions, the internalized cargoes are sorted at (and transported from) the trans-Golgi network/early endosome (TGN/EE) to the vacuole for degradation or recycled back to the plasma membrane. How this occurs at the molecular level remains largely elusive. Here we provide evidence that the ENTH domain-containing protein AtECA4 plays a crucial role in recycling cargoes from the TGN/EE to the plasma membrane...
January 6, 2018: Molecular Plant
https://www.readbyqxmd.com/read/29316441/budding-yeast-has-a-minimal-endomembrane-system
#4
Kasey J Day, Jason C Casler, Benjamin S Glick
The endomembrane system consists of the secretory and endocytic pathways, which communicate by transport to and from the trans-Golgi network (TGN). In mammalian cells, the endocytic pathway includes early, late, and recycling endosomes. In budding yeast, different types of endosomes have been described, but the organization of the endocytic pathway has remained unclear. We performed a spatial and temporal analysis of yeast endosomal markers and endocytic cargoes. Our results indicate that the yeast TGN also serves as an early and recycling endosome...
January 8, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29305335/identification-and-functional-characterization-of-toll-like-receptor-13-from-orange-spotted-grouper-epinephelus-coioides
#5
Yaosi Liang, Xu Ding, Xue Yu, Yu Wang, Ying Zhou, Jianan He, Yu Shi, Yong Zhang, Haoran Lin, Danqi Lu
Toll-like receptors (TLRs) are one of the most important innate immune receptors, which recognize various pathogen-associated molecular patterns from different pathogens and activate the downstream immune response. Mouse TLR13 has been found to recognize a highly conserved sequence from bacterial or viral RNA and activate the myeloid differentiation primary response gene 88-dependent signaling response. The function of teleost tlr13 is still not fully understood, especially its relationship with bacterial RNA...
January 2, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29303993/endolysosomal-cation-channels-and-cancer-a-link-with-great-potential
#6
REVIEW
Christian Grimm, Karin Bartel, Angelika M Vollmar, Martin Biel
The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism...
January 5, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29296614/neuropathology-of-childhood-onset-basal-ganglia-degeneration-caused-by-mutation-of-vac14
#7
Chloe Stutterd, Peter Diakumis, Melanie Bahlo, Miriam Fanjul Fernandez, Richard J Leventer, Martin Delatycki, David Amor, Chung W Chow, Sarah Stephenson, Miriam H Meisler, Catriona Mclean, Paul J Lockhart
Objective: To characterize the clinical features and neuropathology associated with recessive VAC14 mutations. Methods: Whole-exome sequencing was used to identify the genetic etiology of a rapidly progressive neurological disease presenting in early childhood in two deceased siblings with distinct neuropathological features on post mortem examination. Results: We identified compound heterozygous variants in VAC14 in two deceased siblings with early childhood onset of severe, progressive dystonia, and neurodegeneration...
December 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29285934/synthetic-polymeric-mixed-micelles-target-to-lymph-node-triggering-enhanced-cellular-and-humoral-immune-responses
#8
Chenxi Li, Xiaoxu Zhang, Qing Chen, Jiulong Zhang, Wenpan Li, Haiyang Hu, Xiuli Zhao, Mingxi Qiao, Dawei Chen
It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines since antigen presentation and initiation of T cell-mediated immune responses occur primarily at these locations. In this study, amphiphilic diblock copolymer PEOz-PLA combined with carboxylterminalted-Pluronic F127 were used to construct mixed micelles (carboxylated-NPs) for co-delivery of antigen OVA and Toll-like receptor-7 agonist CL264 (carboxylated-NPs/OVA/CL264) to the LN resident DCs. The results showed that the small, sub-60nm size of the self-assembled mixed micelles enables them to rapidly penetrate into lymphatic vessels and reach DLNs after subcutaneous injection...
December 29, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29283386/the-abrogation-of-phosphorylation-plays-a-relevant-role-in-the-ccr5-signalosome-formation-with-natural-antibodies-to-ccr5
#9
Assunta Venuti, Claudia Pastori, Gabriel Siracusano, Rosamaria Pennisi, Agostino Riva, Massimo Tommasino, Maria Teresa Sciortino, Lucia Lopalco
The exposure to CCR5 (CC chemokine receptor 5) specific natural antibodies in vitro produces a Class B β-arrestin2-dependent CCR5 retention with the aid of ERK1, due to the formation of a CCR5 signalosome, which remains stable for at least 48 h. Considering that β-arrestins and MAPKs are receptive to environmental signals, their signal complexes could be one of the key junction for GPCRs internalization related signal transduction. Here, we demonstrate that, in T cells, the phosphorylation status of either CCR5 receptor or ERK1 protein is necessary to drive the internalized receptor into the early endosomes, forming the CCR5 signalosome...
December 28, 2017: Viruses
https://www.readbyqxmd.com/read/29282322/antagonistic-regulation-of-trafficking-to-caenorhabditis-elegans-sensory-cilia-by-a-retinal-degeneration-3-homolog-and-retromer
#10
Luis A Martínez-Velázquez, Niels Ringstad
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...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29281265/responsive-nanomicellar-theranostic-cages-for-metastatic-breast-cancer
#11
Amrutha Manigandan, Vandhana Handi, Niranjana Sri Sundaramoorthy, Ramya Dhandapani, Janani Radhakrishnan, Swaminathan Sethuraman, Anuradha Subramanian
Precluding the progression of metastasis with early-diagnosis of triple-negative breast cancer remains challenging due to lack of targeting specificity with poor diagnostic potential. Herein, an amphipathic chitosan-based targeted nanomicellar theranostics (30-45 nm) comprising doxorubicin-superparamagnetic iron oxide nanoparticles complexes (89.23%) with lower critical micelle concentration (0.1 µg/mL) were developed. Micelles exhibits concentration-based contrast enhancement in MRI (r2 6.27mM-1s-1) and hyperthermia rather than thermal-ablation...
December 27, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29278889/erythromyeloid-derived-trem2-a-major-determinant-of-alzheimer-s-disease-pathology-in-down-syndrome
#12
Ruma Raha-Chowdhury, James W Henderson, Animesh Alexander Raha, Simon R W Stott, Romina Vuono, Simona Foscarin, Liam Wilson, Tiina Annus, Robert Fincham, Kieren Allinson, Vinod Devalia, Robert P Friedland, Anthony Holland, Shahid H Zaman
BACKGROUND: Down syndrome (DS; trisomy 21) individuals have a spectrum of hematopoietic and neuronal dysfunctions, and by the time they reach the age of 40 years, almost all develop Alzheimer's disease (AD) neuropathology which includes senile plaques and neurofibrillary tangles. Inflammation and innate immunity are key players in AD and DS. Triggering receptor expressed in myeloid cells-2 (TREM2) variants have been identified as risk factors for AD and other neurodegenerative diseases...
December 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29277005/landmarks-of-endosomal-remodeling-in-the-early-phase-of-cytomegalovirus-infection
#13
Ljerka Karleuša, Hana Mahmutefendić, Maja Ilić Tomaš, Gordana Blagojević Zagorac, Pero Lučin
Cytomegaloviruses (CMVs) extensively rearrange the cellular membrane system to develop assembly compartment (AC), but the earliest events in this process are poorly characterized. Here, we demonstrate that murine CMV (MCMV) infection restrains endosomal trafficking of cargo molecules that travel along the recycling (TfR and MHC-I) and the late endosomal (EGFR, M6PR, Lamp1) circuit. Internalized cargo accumulates in Arf6-, Rab5-, Rab22A-, and Rab11-positive and Rab35-, Rab8-, and Rab10-negative juxtanuclear endosomes, suggesting the disruption of Arf/Rab regulatory cascade at the stage of sorting endosomes and the endosomal recycling compartment...
December 22, 2017: Virology
https://www.readbyqxmd.com/read/29275387/syndrome-of-x-linked-intellectual-disability-epilepsy-progressive-brain-atrophy-and-large-head-associated-with-slc9a6-mutation
#14
Hansashree Padmanabha, Arushi Gahlot Saini, Jitendra Kumar Sahu, Pratibha Singhi
SLC9A6 gene encodes for a sodium/hydrogen exchanger-6 protein mainly involved in endosomal trafficking and maintaining intraluminal pH. Loss of function mutations in SLC9A6 gene in children has been associated with Christianson syndrome and autism spectrum disorder. We describe a 3-year-old boy with intellectual disability, infantile-onset drug-refractory epilepsy, progressive brain atrophy and large head with a novel missense hemizygous mutation in exon 16 of the SLC9A6 gene on chromosome X. Presence of large head, early developmental regression and progressive cerebral atrophy expand the phenotypic spectrum of SLC9A6 mutations...
December 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29262337/apache-is-an-ap2-interacting-protein-involved-in-synaptic-vesicle-trafficking-and-neuronal-development
#15
Alessandra Piccini, Enrico Castroflorio, Pierluigi Valente, Fabrizia C Guarnieri, Davide Aprile, Caterina Michetti, Mattia Bramini, Giorgia Giansante, Bruno Pinto, Annalisa Savardi, Fabrizia Cesca, Angela Bachi, Angela Cattaneo, Jonathan D Wren, Anna Fassio, Flavia Valtorta, Fabio Benfenati, Silvia Giovedì
Synaptic transmission is critically dependent on synaptic vesicle (SV) recycling. Although the precise mechanisms of SV retrieval are still debated, it is widely accepted that a fundamental role is played by clathrin-mediated endocytosis, a form of endocytosis that capitalizes on the clathrin/adaptor protein complex 2 (AP2) coat and several accessory factors. Here, we show that the previously uncharacterized protein KIAA1107, predicted by bioinformatics analysis to be involved in the SV cycle, is an AP2-interacting clathrin-endocytosis protein (APache)...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29246902/identification-of-the-coagulation-factor-viia-integrin-binding-site-required-for-pro-angiogenic-par2-signaling
#16
Andrea S Rothmeier, Enbo Liu, Sagarika Chakrabarty, Jennifer Disse, Barbara M Mueller, Henrik Østergaard, Wolfram Ruf
The tissue factor (TF) pathway serves both hemostasis and cell signaling, but how cells control these divergent functions of TF remains incompletely understood. TF is the receptor and scaffold of coagulation proteases cleaving protease activated receptor (PAR) 2 that plays pivotal roles in angiogenesis and tumor development. Here we demonstrate that coagulation factor (F) VIIa elicits TF cytoplasmic domain-dependent pro-angiogenic cell signaling independent of the alternative PAR2 activator matriptase. We identify a Lys-Gly-Glu (KGE) integrin binding motif in the FVIIa protease domain that is required for association of the TF-FVIIa complex with the active conformer of integrin β1...
December 15, 2017: Blood
https://www.readbyqxmd.com/read/29237845/human-cytomegalovirus-replication-is-inhibited-by-the-autophagy-inducing-compounds-trehalose-and-smer28-through-distinctively-different-mechanisms
#17
Alex E Clark, Maite Sabalza, Philip L S M Gordts, Deborah H Spector
Human Cytomegalovirus (HCMV) is the top viral cause of birth defects worldwide, and current therapies have high toxicity. We previously published that the mTOR-independent autophagy-inducing disaccharide trehalose inhibits HCMV replication in multiple cell types. Here, we examine the mechanism of inhibition and introduce the autophagy inducer SMER28 as an additional inhibitor of HCMV acting through a different mechanism. We find that trehalose induces vacuolation and acidification of vacuoles, and that debris, including debris consistent in appearance with abnormal virions, is present in multivesicular bodies...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237821/sequential-actions-of-phosphatidylinositol-phosphates-regulate-phagosome-lysosome-fusion
#18
Andreas Jeschke, Albert Haas
Phagosomes mature into phagolysosomes by sequential fusion with early endosomes, late endosomes, and lysosomes. Phagosome-with-lysosome fusion (PLF) results in the delivery of lysosomal hydrolases into phagosomes and in digestion of the cargo. The machinery that drives PLF has been little investigated. Using a cell-free system, we recently identified the phosphoinositide lipids (PIPs) phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 4-phosphate [PI(4)P] as regulators of PLF. We now report the identification and the PIP requirements of four distinct sub-reactions of PLF...
December 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29236694/dynamics-of-phosphoinositide-conversion-in-clathrin-mediated-endocytic-traffic
#19
Kangmin He, Robert Marsland Iii, Srigokul Upadhyayula, Eli Song, Song Dang, Benjamin R Capraro, Weiming Wang, Wesley Skillern, Raphael Gaudin, Minghe Ma, Tom Kirchhausen
Vesicular carriers transport proteins and lipids from one organelle to another, recognizing specific identifiers for the donor and acceptor membranes. Two important identifiers are phosphoinositides and GTP-bound GTPases, which provide well-defined but mutable labels. Phosphatidylinositol and its phosphorylated derivatives are present on the cytosolic faces of most cellular membranes. Reversible phosphorylation of its headgroup produces seven distinct phosphoinositides. In endocytic traffic, phosphatidylinositol-4,5-biphosphate marks the plasma membrane, and phosphatidylinositol-3-phosphate and phosphatidylinositol-4-phosphate mark distinct endosomal compartments...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29229837/early-endosome-as-a-pathogenic-target-for-antiphosphatidylethanolamine-antibodies
#20
Songwang Hou, Heike Fölsch, Ke Ke, Joan Cook Mills, Rosalind Ramsey-Goldman, Ming Zhao
Phosphatidylethanolamine (PE) is a major phospholipid species with important roles in membrane trafficking and reorganization. Accumulating clinical data indicate that the presence of circulating antibodies against PE is positively correlated with the symptoms of antiphospholipid syndromes (APS), including thrombosis and repeated pregnancy loss. However, PE is generally sequestered inside a normal resting cell, and the mechanism by which circulating anti-PE antibodies access cellular PE remains unknown. The studies presented here were conducted with synthetic PE-binding agents, plasma samples from patients with anti-PE autoimmunity, and purified anti-PE antibodies...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
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