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https://www.readbyqxmd.com/read/28529827/deviant-lysosomal-ca-2-signalling-in-neurodegeneration-an-introduction
#1
Sandip Patel
Lysosomes are key acidic Ca(2+) stores. The principle Ca(2+)-permeable channels of the lysosome are TRP mucolipins (TRPMLs) and NAADP-regulated two-pore channels (TPCs). Recent studies, reviewed in this collection, have linked numerous neurodegenerative diseases to both gain and loss of function of TRPMLs/TPCs, as well as to defects in acidic Ca(2+) store content. These diseases span rare lysosomal storage disorders such as Mucolipidosis Type IV and Niemann-Pick disease, type C, through to more common ones such as Alzheimer and Parkinson disease...
June 1, 2016: Messenger
https://www.readbyqxmd.com/read/28528219/the-ongoing-saga-of-the-mechanism-s-of-mhc-class-i-restricted-cross-presentation
#2
Jeff E Grotzke, Debrup Sengupta, Qiao Lu, Peter Cresswell
Cross-presentation is an MHC-I antigen processing pathway that results in the presentation of peptides from exogenous viral, bacterial, parasitic, and tumor antigens and ultimately leads to priming of naïve CD8(+) T cells. This process involves several cellular compartments and multiple components. Successful generation of MHC-I-peptide complexes requires that these components act together in a coordinated fashion. We discuss recent findings on the source of MHC-I, the role of the TAP transporter, the importance of intracellular trafficking events, mechanisms of antigen access the cytosol, and how innate immune signals can affect presentation, with an emphasis on how these pathways compare to conventional antigen presentation and how they correlate with existing data...
May 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28526875/endophilinas-regulate-endosomal-sorting-of-bdnf-trkb-to-mediate-survival-signaling-in-hippocampal-neurons
#3
Katja Burk, John D Murdoch, Siona Freytag, Melanie Koenig, Vinita Bharat, Ronja Markworth, Susanne Burkhardt, Andre Fischer, Camin Dean
The sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs in sorting of activated BDNF-TrkB receptors into late endosomal compartments. Mice lacking all three EndophilinAs accumulate Rab7-positive late endosomes. Moreover, EndophilinAs are differentially localized to, co-traffic with, and tubulate, distinct endosomal compartments: In response to BDNF, EndophilinA2 is recruited to both early and late endosomes, EndophilinA3 is recruited to Lamp1-positive late endosomes, and co-trafficks with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalizes at lower levels with endosomes...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28525743/bromodomain-protein-brd4-is-a-transcriptional-repressor-of-autophagy-and-lysosomal-function
#4
Jun-Ichi Sakamaki, Simon Wilkinson, Marcel Hahn, Nilgun Tasdemir, Jim O'Prey, William Clark, Ann Hedley, Colin Nixon, Jaclyn S Long, Maria New, Tim Van Acker, Sharon A Tooze, Scott W Lowe, Ivan Dikic, Kevin M Ryan
Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28522156/the-role-of-erbb-receptors-in-infection
#5
REVIEW
Jemima Ho, David L Moyes, Mahvash Tavassoli, Julian R Naglik
Members of the epidermal growth factor receptor family (ErbB family) possess a wide distribution and diverse functions ranging from cellular growth to migration and apoptosis. Though highly implicated in a variety of cancers, their involvement in infectious disease is less recognised. A growing body of evidence now highlights the importance of the ErbB family in a variety of infections. Their role as growth factor receptors, along with other characteristics, such as surface expression and continuous intracellular trafficking, make this receptor family ideally placed for exploitation by pathogens...
May 15, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28521278/scaffold-protein-jlp-mediates-tcr-initiated-cd4-t-cell-activation-and-cd154-expression
#6
Qi Yan, Cheng Yang, Qiang Fu, Zhaowei Chen, Shan Liu, Dou Fu, Rahmat N Rahman, Ryota Nakazato, Katsuji Yoshioka, Sam K P Kung, Guohua Ding, Huiming Wang
CD4(+) T-cell activation and its subsequent induction of CD154 (CD40 ligand, CD40L) expression are pivotal in shaping both the humoral and cellular immune responses. Scaffold protein JLP regulates signal transduction pathways and molecular trafficking inside cells, thus represents a critical component in maintaining cellular functions. Its role in regulating CD4(+) T-cell activation and CD154 expression, however, is unclear. Here, we demonstrated expression of JLP in mouse tissues of lymph nodes, thymus, spleen, and also CD4(+) T cells...
May 15, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28521260/exocytosis-for-endosymbiosis-membrane-trafficking-pathways-for-development-of-symbiotic-membrane-compartments
#7
REVIEW
Maria J Harrison, Sergey Ivanov
During endosymbiosis with arbuscular mycorrhizal fungi or rhizobial bacteria, the microbial symbionts are housed within membrane-bound compartments in root cortex or nodule cells respectively. Their development involves polarized deposition of membrane around the symbionts as they enter the cells and the membranes show functional specialization, including transporters that mediate nutrient transfer between host and symbiont. The cellular changes associated with development of these compartments point to membrane deposition via exocytosis and over the past few years, researchers have uncovered several proteins within the exocytotic pathway that are required for development of endosymbiotic membrane compartments...
May 15, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28518105/murine-lymphocyte-labeling-by-64cu-antibody-receptor-targeting-for-in-vivo-cell-trafficking-by-pet-ct
#8
Sabrina H L Hoffmann, Andreas Maurer, Dorothea I Reck, Gerald Reischl, Bernd J Pichler, Manfred Kneilling, Christoph M Griessinger
This protocol illustrates the production of (64)Cu and the chelator conjugation/radiolabeling of a monoclonal antibody (mAb) followed by murine lymphocyte cell culture and (64)Cu-antibody receptor targeting of the cells. In vitro evaluation of the radiolabel and non-invasive in vivo cell tracking in an animal model of an airway delayed-type hypersensitivity reaction (DTHR) by PET/CT are described. In detail, the conjugation of a mAb with the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is shown...
April 29, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28515232/the-nuclear-export-factor-crm1-controls-juxta-nuclear-microtubule-dependent-virus-transport
#9
I-Hsuan Wang, Christoph J Burckhardt, Artur Yakimovich, Matthias K Morf, Urs F Greber
Transport of large cargo through the cytoplasm requires motor proteins and polarized filaments. Viruses that replicate in the nucleus of post-mitotic cells use microtubules and the dynein/dynactin motor to traffic to the nuclear membrane, and deliver their genome through nuclear pore complexes (NPCs) into the nucleus. How virus particles (virions) or cellular cargo are transferred from microtubules to the NPC is unknown. Here, we analyzed trafficking of incoming cytoplasmic adenoviruses by single particle tracking and super-resolution microscopy...
May 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28515229/unique-cell-biological-profiles-of-retinal-disease-causing-missense-mutations-in-the-polarity-protein-crumbs
#10
Milena Pellikka, Ulrich Tepass
Mutations in human CRB1 are a major cause of retinal disease that lead to blindness. CRB1 is a transmembrane protein found in the inner segment of photoreceptor cells (PRCs) and the apical membrane of Müller glia. The function of the extracellular region of CRB1 is poorly understood although more than 80 disease-causing missense mutations have been mapped to it. We have recreated four mutations in Drosophila Crumbs (Crb) that affect different extracellular domains. Crb regulates epithelial polarity and growth, and contributes to PRC differentiation and survival...
May 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28514713/pattern-recognition-receptors-and-coordinated-cellular-pathways-involved-in-tuberculosis-immunopathogenesis-emerging-concepts-and-perspectives
#11
REVIEW
Abhishek Mishra, Shamim Akhtar, Chinnaswamy Jagannath, Arshad Khan
Pattern Recognition Receptors (PRRs) play a central role in the recognition of numerous pathogens, including Mycobacterium tuberculosis, resulting in activation of innate and adaptive immune responses. Besides Toll Like Receptors, C-type Lectin Receptors and Nod Like Receptors are now being recognized for their involvement in inducing immune response against M. tuberculosis infection. Although, a functional redundancy of the PRRs has also been reported in many studies, emerging evidences support the notion that a cooperative and coordinated response generated by these receptors is critical to sustain the full immune control of M...
May 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28512187/neutral-competition-for-drosophila-follicle-and-cyst-stem-cell-niches-requires-vesicle-trafficking-genes
#12
Matthew S Cook, Coralie Cazin, Marc Amoyel, Shinya Yamamoto, Erika Bach, Todd Nystul
The process of selecting for cellular fitness through competition plays a critical role in both development and disease. The germarium, a structure at the tip of the ovariole of a Drosophila ovary, contains two follicle stem cells (FSCs) that undergo neutral competition for the stem cell niche. Using the FSCs as a model, we performed a genetic screen through a collection of 126 mutants in essential genes on the X chromosome to identify candidates that increase or decrease competition for the FSC niche. We identified approximately 55% and 6% of the mutations screened as putative FSC hypo- or hypercompetitors, respectively...
May 16, 2017: Genetics
https://www.readbyqxmd.com/read/28508261/functional-roles-of-the-pepper-leucine-rich-repeat-protein-and-its-interactions-with-pathogenesis-related-and-hypersensitive-induced-proteins-in-plant-cell-death-and-immunity
#13
REVIEW
Jeum Kyu Hong, In Sun Hwang, Byung Kook Hwang
Pepper leucine-rich repeat protein (CaLRR1) interacts with defense response proteins to regulate plant cell death and immunity. This review highlights the current understanding of the molecular functions of CaLRR1 and its interactor proteins. Plant cell death and immune responses to microbial pathogens are controlled by complex and tightly regulated molecular signaling networks. Xanthomonas campestris pv. vesicatoria (Xcv)-inducible pepper (Capsicum annuum) leucine-rich repeat protein 1 (CaLRR1) serves as a molecular marker for plant cell death and immunity signaling...
May 15, 2017: Planta
https://www.readbyqxmd.com/read/28507811/adoptive-natural-killer-cell-therapy-is-effective-in-reducing-pulmonary-metastasis-of-ewing-sarcoma
#14
Alexander A Tong, Hasan Hashem, Saada Eid, Frederick Allen, Daniel Kingsley, Alex Y Huang
The survival of patients with metastatic or relapsed Ewing sarcoma (ES) remains dismal despite intensification of combination chemotherapy and radiotherapy, precipitating the need for novel alternative therapies with minimal side effects. Natural killer (NK) cells are promising additions to the field of cellular immunotherapy. Adoptive NK cell therapy has shown encouraging results in hematological malignancies. Despite these initial promising successes, however, NK cell therapy for solid tumors remains to be investigated using in vivo tumor models...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506430/george-e-palade-memorial-lecture-my-life-in-pancreatic-research-unexpected-results-may-open-the-door
#15
REVIEW
Makoto Otsuki
The Palade Prize is the most distinguished award of the IAP for achievement in pancreatic research. It is named after George E. Palade, who in 1974 was awarded the Nobel Prize for his work on protein trafficking in pancreatic acinar cells. It is a great honor to be awarded the 2016 Palade Prize. While I was in graduate school, I was conducting research on hypothalamo-pituitary-thyroid axis; after finishing graduate school, I began research on amylase isoenzymes. This was the first step of my pancreatic research...
May 6, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28505157/structurally-optimized-analogs-of-the-retrograde-trafficking-inhibitor-retro-2cycl-limit-leishmania-infections
#16
Evan Craig, Charles-Eugene Huyghues-Despointes, Chun Yu, Emma L Handy, Jason K Sello, Peter E Kima
In infected mammalian cells, Leishmania parasites reside within specialized compartments called parasitophorous vacuoles (LPVs). We have previously shown that Retro-2, a member of a novel class of small retrograde pathway inhibitors caused reduced LPV sizes and lower parasite numbers during experimental L. mexicana sp. infections. The purpose of this study was to determine if structural analogs of Retro-2cycl reported to have superior potency in the inhibition of retrograde pathway-dependent phenomena (i.e...
May 15, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28504698/dendritic-cells-enter-lymph-vessels-by-hyaluronan-mediated-docking-to-the-endothelial-receptor-lyve-1
#17
Louise A Johnson, Suneale Banerji, William Lawrance, Uzi Gileadi, Gennaro Prota, Kayla A Holder, Yaowaluck M Roshorm, Tomáš Hanke, Vincenzo Cerundolo, Nicholas W Gale, David G Jackson
Trafficking of tissue dendritic cells (DCs) via lymph is critical for the generation of cellular immune responses in draining lymph nodes (LNs). In the current study we found that DCs docked to the basolateral surface of lymphatic vessels and transited to the lumen through hyaluronan-mediated interactions with the lymph-specific endothelial receptor LYVE-1, in dynamic transmigratory-cup-like structures. Furthermore, we show that targeted deletion of the gene Lyve1, antibody blockade or depletion of the DC hyaluronan coat not only delayed lymphatic trafficking of dermal DCs but also blunted their capacity to prime CD8(+) T cell responses in skin-draining LNs...
May 15, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28504462/endocytic-activity-of-hiv-1-vpu-phosphoserine-dependent-interactions-with-clathrin-adaptors
#18
Charlotte A Stoneham, Rajendra Singh, Xiaofei Jia, Yong Xiong, John Guatelli
HIV-1 Vpu modulates cellular transmembrane proteins to optimize viral replication and provide immune-evasion, triggering ubiquitin-mediated degradation of some targets but also modulating endosomal trafficking to deplete them from the plasma membrane. Interactions between Vpu and the heterotetrameric clathrin adaptors AP-1 and AP-2 have been described, yet the molecular basis and functional roles of such interactions are incompletely defined. To investigate the trafficking signals encoded by Vpu, we fused the cytoplasmic domain (CD) of Vpu to the extracellular and transmembrane domains of the CD8 α-chain...
May 14, 2017: Traffic
https://www.readbyqxmd.com/read/28501614/shaping-mitochondrial-dynamics-the-role-of-camp-signalling
#19
Giulietta Di Benedetto, Andrea Gerbino, Konstantinos Lefkimmiatis
In recent years, our idea of mitochondria evolved from "mere" energy and metabolite producers to key regulators of many cellular functions. In order to preserve and protect their functional status, these organelles engage a number of dynamic processes that allow them to decrease accumulated burden and maintain their homeostasis. Indeed, mitochondria can unite (fusion), divide (fission), position themselves strategically in the cell (motility/trafficking) and if irreversibly damaged or dysfunctional eliminated (mitophagy)...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28500977/endocytosis-and-intracellular-traffic-of-cholesterol-pdmaema-liposome-complexes-in-human-epithelial-like-cells
#20
F Szymanowski, A A Hugo, P Alves, P N Simões, A Gómez-Zavaglia, Pablo F Pérez
Liposomes are generally used as delivery systems, as they are capable of encapsulating a wide variety of molecules (i.e. plasmids, recombinant proteins, therapeutic drugs). However, liposomal drug delivery have to fulfill different requirements, such as the effective internalization by the target cells and avoidance of the degradative activity of the intracellular compartments. The use of polymer lipid complexes (PLCs), by including different polymers in the liposome formulation, could improve internalization and intracellular release of drugs...
May 1, 2017: Colloids and Surfaces. B, Biointerfaces
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