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Adaptor protein 1

Nurbek Mambetsariev, Wai W Lin, Alicia M Wallis, Laura L Stunz, Gail A Bishop
The adaptor protein TNF receptor-associated factor 3 (TRAF3) is a critical regulator of B lymphocyte survival. B cell-specific TRAF3 deficiency results in enhanced viability and is associated with development of lymphoma and multiple myeloma. We show that TRAF3 deficiency led to induction of two proteins important for glucose metabolism, Glut1 and Hexokinase 2 (HXK2). This was associated with increased glucose uptake. In the absence of TRAF3, anaerobic glycolysis and oxidative phosphorylation were increased in B cells without changes in mitochondrial mass or reactive oxygen species...
October 18, 2016: Scientific Reports
Ming-Fong Chang, Jung-Hsien Hsieh, Hao Chiang, Hung-Wei Kan, Cho-Min Huang, Luke Chellis, Bo-Shiou Lin, Shi-Chuen Miaw, Chun-Liang Pan, Chi-Chao Chao, Sung-Tsang Hsieh
Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP)...
October 17, 2016: Scientific Reports
Marie-Laure Specq, Mélisande Bourgoin-Heck, Nathalie Samson, François Corbin, Christian Gestreau, Maxime Richer, Hazim Kadhim, Jean-Paul Praud
Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. Moderate HB can induce acute neurological disorders while severe HB has been linked to a higher incidence of apneas of prematurity. The present study aimed to test the hypothesis that even moderate HB disrupts cardiorespiratory control in preterm lambs. Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. At day 5 of life, moderate HB (150-250 μmol/L) was induced during 17 h in the HB group after which cardiorespiratory control as well as laryngeal and pulmonary chemoreflexes were assessed during baseline recordings and during hypoxia...
2016: Frontiers in Physiology
Marlen Thiere, Stefanie Kliche, Bettina Müller, Jan Teuber, Isabell Nold, Oliver Stork
Integrin-mediated cell adhesion and signaling is of critical importance for neuronal differentiation. Recent evidence suggests that an "inside-out" activation of β1-integrin, similar to that observed in hematopoietic cells, contributes to the growth and branching of dendrites. In this study, we investigated the role of the hematopoietic adaptor protein adhesion and degranulation promoting adapter protein (ADAP) in these processes. We demonstrate the expression of ADAP in the developing and adult nervous hippocampus, and in outgrowing dendrites of primary hippocampal neurons...
2016: Frontiers in Molecular Neuroscience
Roshan J Thapa, Justin P Ingram, Katherine B Ragan, Shoko Nogusa, David F Boyd, Asiel A Benitez, Haripriya Sridharan, Rachelle Kosoff, Maria Shubina, Vanessa J Landsteiner, Mark Andrake, Peter Vogel, Luis J Sigal, Benjamin R tenOever, Paul G Thomas, Jason W Upton, Siddharth Balachandran
Influenza A virus (IAV) is an RNA virus that is cytotoxic to most cell types in which it replicates. IAV activates the host kinase RIPK3, which induces cell death via parallel pathways of necroptosis, driven by the pseudokinase MLKL, and apoptosis, dependent on the adaptor proteins RIPK1 and FADD. How IAV activates RIPK3 remains unknown. We report that DAI (ZBP1/DLM-1), previously implicated as a cytoplasmic DNA sensor, is essential for RIPK3 activation by IAV. Upon infection, DAI recognizes IAV genomic RNA, associates with RIPK3, and is required for recruitment of MLKL and RIPK1 to RIPK3...
October 8, 2016: Cell Host & Microbe
Yi Zhou, Wenjuan Yu, Huan Zhong, Jianlin Li, Hongxia Li, Feng He, Jie Zhou, Yongkai Tang, Juhua Yu, Fan Yu
Common carp (Cyprinus carpio) is a widespread freshwater fish and economically important species in China and other East Asian countries. Recent studies suggest that insulin can alter the expression of immune genes and, thus, can be regarded as an immunomodulatory hormone. To understand the mechanism of the immune response to insulin, we performed a comparative RNA-seq transcriptome analysis using livers from common carp injected with insulin (5 μg/g bodyweight) or saline as a control. After filtering the low-quality reads and removing the adaptors, the clean raw reads were assembled into 60,421 unigenes with mean length of 746...
October 11, 2016: Fish & Shellfish Immunology
Elvira Khialeeva, Ellen M Carpenter
The reelin signaling pathway has been established as an important regulator of cell migration during development of the central nervous system, and disruptions in reelin signaling alter the positioning of many types of neurons in the developing central nervous system. Reelin is a large extracellular matrix glycoprotein and governs cell migration through activation of multiple intracellular signaling events via the receptors ApoE receptor 2 (ApoER2) and Very Low Density Lipoprotein Receptor (VLDLR), and the intracellular adaptor protein Disabled-1 (Dab1)...
October 14, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Tetsuya Kimura, Shigeyuki Nada, Noriko Takegahara, Tatsusada Okuno, Satoshi Nojima, Sujin Kang, Daisuke Ito, Keiko Morimoto, Takashi Hosokawa, Yoshitomo Hayama, Yuichi Mitsui, Natsuki Sakurai, Hana Sarashina-Kida, Masayuki Nishide, Yohei Maeda, Hyota Takamatsu, Daisuke Okuzaki, Masaki Yamada, Masato Okada, Atsushi Kumanogoh
Macrophages play crucial roles in host defence and tissue homoeostasis, processes in which both environmental stimuli and intracellularly generated metabolites influence activation of macrophages. Activated macrophages are classified into M1 and M2 macrophages. It remains unclear how intracellular nutrition sufficiency, especially for amino acid, influences on macrophage activation. Here we show that a lysosomal adaptor protein Lamtor1, which forms an amino-acid sensing complex with lysosomal vacuolar-type H(+)-ATPase (v-ATPase), and is the scaffold for amino acid-activated mTORC1 (mechanistic target of rapamycin complex 1), is critically required for M2 polarization...
October 12, 2016: Nature Communications
Agata Mata, Laura Urrea, Silvia Vilches, Franc Llorens, Katrin Thüne, Juan-Carlos Espinosa, Olivier Andréoletti, Alejandro M Sevillano, Juan María Torres, Jesús Rodríguez Requena, Inga Zerr, Isidro Ferrer, Rosalina Gavín, José Antonio Del Río
Reelin is an extracellular glycoprotein involved in key cellular processes in developing and adult nervous system, including regulation of neuronal migration, synapse formation, and plasticity. Most of these roles are mediated by the intracellular phosphorylation of disabled-1 (Dab1), an intracellular adaptor molecule, in turn mediated by binding Reelin to its receptors. Altered expression and glycosylation patterns of Reelin in cerebrospinal and cortical extracts have been reported in Alzheimer's disease...
October 10, 2016: Molecular Neurobiology
John D Murdoch, Christine M Rostosky, Sindhuja Gowrisankaran, Amandeep S Arora, Sandra-Fausia Soukup, Ramon Vidal, Vincenzo Capece, Siona Freytag, Andre Fischer, Patrik Verstreken, Stefan Bonn, Nuno Raimundo, Ira Milosevic
Endophilin-A, a well-characterized endocytic adaptor essential for synaptic vesicle recycling, has recently been linked to neurodegeneration. We report here that endophilin-A deficiency results in impaired movement, age-dependent ataxia, and neurodegeneration in mice. Transcriptional analysis of endophilin-A mutant mice, complemented by proteomics, highlighted ataxia- and protein-homeostasis-related genes and revealed upregulation of the E3-ubiquitin ligase FBXO32/atrogin-1 and its transcription factor FOXO3A...
October 5, 2016: Cell Reports
Xinchun Ye, Delian Kong, Jun Wang, Tauheed Ishrat, Hongjuan Shi, Xiaohui Ding, Guiyun Cui, Fang Hua
Myeloid differentiation primary-response protein-88 (MyD88) is one of adaptor proteins mediating Toll-like receptors (TLRs) signaling. Activation of MyD88 results in the activation of nuclear factor kappa B (NFκB) and the increase of inflammatory responses. Evidences have demonstrated that TLRs signaling contributes to cerebral ischemia/reperfusion (I/R) injury. However, the role of MyD88 in this mechanism of action is disputed and needs to be clarified. In the present study, in a mouse model of cerebral I/R, we examined the activities of NFκB and interferon factor-3 (IRF3), and the inflammatory responses in ischemic brain tissue using ELISA, Western blots, and real-time PCR...
October 4, 2016: Biochemical and Biophysical Research Communications
Miranda Arnold, Rebecca Cross, Kaela S Singleton, Stephanie Zlatic, Christopher Chapleau, Ariana P Mullin, Isaiah Rolle, Carlene C Moore, Anne Theibert, Lucas Pozzo-Miller, Victor Faundez, Jennifer Larimore
AGAP1 is an Arf1 GTPase activating protein that interacts with the vesicle-associated protein complexes adaptor protein 3 (AP-3) and Biogenesis of Lysosome Related Organelles Complex-1 (BLOC-1). Overexpression of AGAP1 in non-neuronal cells results in an accumulation of endosomal cargoes, which suggests a role in endosome-dependent traffic. In addition, AGAP1 is a candidate susceptibility gene for two neurodevelopmental disorders, autism spectrum disorder (ASD) and schizophrenia (SZ); yet its localization and function in neurons have not been described...
2016: Frontiers in Cellular Neuroscience
Han-Gyu Choi, Seunga Choi, Yong Woo Back, Hye-Soo Park, Hyun Shik Bae, Chul Hee Choi, Hwa-Jung Kim
Macrophages constitute the first line of defense against Mycobacterium tuberculosis and are critical in linking innate and adaptive immunity. Therefore, the identification and characterization of mycobacterial proteins that modulate macrophage function are essential for understanding tuberculosis pathogenesis. In this study, we identified the novel macrophage-activating protein, Rv2882c, from M. tuberculosis culture filtrate proteins. Recombinant Rv2882c protein activated macrophages to secrete pro-inflammatory cytokines and express co-stimulatory and major histocompatibility complex molecules via Toll-like receptor 4, myeloid differentiation primary response protein 88, and Toll/IL-1 receptor-domain-containing adaptor inducing IFN-beta...
2016: PloS One
Toru Takahashi, Kazuhiro Nakaso, Yosuke Horikoshi, Takehiko Hanaki, Miho Yamakawa, Masato Nakasone, Yoshinori Kitagawa, Taisuke Koike, Tatsuya Matsura
BACKGROUND: Vitamin E (VE, α-tocopherol) is a fat-soluble vitamin and is well known as an antioxidant. A deficiency in VE induces oxidative stress in the brain and causes motor and memory dysfunction. The consumption of a VE-rich diet has been given much attention in recent years, in regards to anti-aging and the prevention of age-related neuronal disorders. METHODS: A VE-deficient mouse model was prepared by feeding the animals a diet lacking VE. In addition, to evaluate the effect of VE-containing rice bran (RB) on VE deficiency, a diet including RB was also provided...
September 2016: Yonago Acta Medica
Jeffrey F Ellena, Wen Xiong, Xiaolin Zhao, Narasimhamurthy Shanaiah, Daniel G S Capelluto
Efficient trafficking of ubiquitinated receptors (cargo) to endosomes requires the recruitment of adaptor proteins that exhibit ubiquitin-binding domains for recognition and transport. Tom1 is an adaptor protein that not only associates with ubiquitinated cargo but also represents a phosphoinositide effector during specific bacterial infections. This phosphoinositide-binding property is associated with its N-terminal Vps27, Hrs, STAM (VHS) domain. Despite its biological relevance, there are no resonance assignments of Tom1 VHS available that can fully characterize its molecular interactions...
October 4, 2016: Biomolecular NMR Assignments
Gaurav Shrivastava, Moisés León-Juárez, Julio García-Cordero, David Eduardo Meza-Sánchez, Leticia Cedillo-Barrón
A complex interplay between pathogen and host determines the immune response during viral infection. A set of cytosolic sensors are expressed by immune cells to detect viral infection. NOD-like receptors (NLRs) comprise a large family of intracellular pattern recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed inflammasomes, which induce downstream immune responses to specific pathogens, environmental stimuli, and host cell damage. Inflammasomes are composed of cytoplasmic sensor molecules such as NLRP3 or absent in melanoma 2 (AIM2), the adaptor protein ASC (apoptosis-associated speck-like protein containing caspase recruitment domain), and the effector protein procaspase-1...
October 3, 2016: Immunologic Research
Tatsuro Iso, Takafumi Suzuki, Liam Baird, Masayuki Yamamoto
The transcription factor Nrf2 (NF-E2-related-factor-2) is essential for the oxidative and electrophilic stress responses. Keap1 (Kelch-like-ECH-associated-protein-1), an adaptor for a Cullin-3 (Cul3)-based ubiquitin ligase, regulates Nrf2 activity through proteasomal degradation, and acts as a sensor for oxidative and electrophilic stresses. The Keap1-Cul3 complex is a critical regulator of the cellular Nrf2 level, yet quantitative information regarding their endogenous intracellular concentrations in homeostatic conditions and during stress responses is unknown...
October 3, 2016: Molecular and Cellular Biology
Arpita Sen, Ligia Acosta-Sampson, Christopher G Alvaro, Jonathan S Ahn, Jamie H D Cate, Jeremy Thorner
: When expressed in Saccharomyces cerevisiae using either of two constitutive yeast promoters (PGK1prom and CCW12prom), the transporters CDT-1 and CDT-2 from the filamentous fungus Neurospora crassa are able to catalyze, respectively, active transport and facilitated diffusion of cellobiose (and, for CDT-2, also xylan and its derivatives). In S. cerevisiae, endogenous permeases are removed from the plasma membrane by clathrin-mediated endocytosis and are marked for internalization through ubiquitinylation catalyzed by Rsp5, a HECT class ubiquitin:protein ligase (E3)...
September 30, 2016: Applied and Environmental Microbiology
Nagat Mohammed, Maria Ceprián, Laura Jimenez, M Ruth Pazos, Jose Martínez-Orgado
BACKGROUND: A relevant therapeutic time window (TTW) is an important criterion for considering the clinical relevance of a substance preventing newborn hypoxic-ischemic (HI) brain damage. OBJECTIVE: to test the TTW of the neuroprotective effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn HI brain damage. METHOD: 9-10 day-old C57BL6 mice underwent a HI insult (10% oxygen for 90 min after left carotid artery electrocoagulation)...
September 27, 2016: CNS & Neurological Disorders Drug Targets
Nina Tang, Juan Ma, Ke Si Wang, Chunliu Mi, Ying Lv, Lian Xun Piao, Guang Hua Xu, Xuezheng Li, Jung Joon Lee, Xuejun Jin
Nuclear factor-kappa B (NF-κB) has been reported to play a pivotal role in many physiological processes including inflammation, apoptosis, and angiogenesis. We discovered a potent natural NF-κB inhibitor, dihydromyricetin, from the traditional herb Ampelopsis grossedentata, which has a long history of use in food and medicine. In this study, we demonstrated the effect of dihydromyricetin on NF-κB activation in TNF-α-induced HeLa cells. Dihydromyricetin was found to markedly inhibit the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα), and subsequent nuclear translocation of p65...
November 2016: Molecular and Cellular Biochemistry
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