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https://www.readbyqxmd.com/read/27933291/endocytosis-and-physiology-insights-from-disabled-2-deficient-mice
#1
REVIEW
Wensi Tao, Robert Moore, Elizabeth R Smith, Xiang-Xi Xu
Disabled-2 (Dab2) is a clathrin and cargo binding endocytic adaptor protein, and cell biology studies revealed that Dab2 plays a role in cellular trafficking of a number of transmembrane receptors and signaling proteins. A PTB/PID domain located in the N-terminus of Dab2 binds the NPXY motif(s) present at the cytoplasmic tails of certain transmembrane proteins/receptors. The membrane receptors reported to bind directly to Dab2 include LDL receptor and its family members LRP1 and LRP2 (megalin), growth factor receptors EGFR and FGFR, and the cell adhesion receptor beta1 integrin...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27931217/lrp1-modulates-the-microglial-immune-response-via-regulation-of-jnk-and-nf-%C3%AE%C2%BAb-signaling-pathways
#2
Longyu Yang, Chia-Chen Liu, Honghua Zheng, Takahisa Kanekiyo, Yuka Atagi, Lin Jia, Daxin Wang, Aurelie N'songo, Dan Can, Huaxi Xu, Xiao-Fen Chen, Guojun Bu
BACKGROUND: Neuroinflammation is characterized by microglial activation and the increased levels of cytokines and chemokines in the central nervous system (CNS). Recent evidence has implicated both beneficial and toxic roles of microglia when over-activated upon nerve injury or in neurodegenerative diseases, including Alzheimer's disease (AD). The low-density lipoprotein receptor-related protein 1 (LRP1) is a major receptor for apolipoprotein E (apoE) and amyloid-β (Aβ), which play critical roles in AD pathogenesis...
December 8, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27924190/network-analysis-of-human-post-mortem-microarrays-reveals-novel-genes-micrornas-and-mechanistic-scenarios-of-potential-importance-in-fighting-huntington-s-disease
#3
Sreedevi Chandrasekaran, Danail Bonchev
Huntington's disease is a progressive neurodegenerative disorder characterized by motor disturbances, cognitive decline, and neuropsychiatric symptoms. In this study, we utilized network-based analysis in an attempt to explore and understand the underlying molecular mechanism and to identify critical molecular players of this disease condition. Using human post-mortem microarrays from three brain regions (cerebellum, frontal cortex and caudate nucleus) we selected in a four-step procedure a seed set of highly modulated genes...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27849881/239-lrp1-an-endocytic-vesicle-trafficking-protein-associated-with-chd-an-unexplored-pathway
#4
Jiuann-Huey Lin, Anupma Jha, Jacob McClreary, Cecilia Lo
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27833152/selenium-binding-lactoferrin-is-taken-into-corneal-epithelial-cells-by-a-receptor-and-prevents-corneal-damage-in-dry-eye-model-animals
#5
Akihiro Higuchi, Hiroyoshi Inoue, Yoshio Kaneko, Erina Oonishi, Kazuo Tsubota
The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases including dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy of Se-lactoferrin eye drops in the tobacco smoke exposure rat dry eye model and short-term rabbit dry eye model, although Diquas eye drops were only effective in the short-term rabbit dry eye model...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27829865/improvement-of-electroacupuncture-on-app-ps1-transgenic-mice-in-spatial-learning-and-memory-probably-due-to-expression-of-a%C3%AE-and-lrp1-in-hippocampus
#6
Xin Wang, Yanhuan Miao, Jiawula Abulizi, Fu Li, Yuping Mo, Weiguo Xue, Zhigang Li
Objectives. To explore the alterations of β-amyloid (Aβ) and low density lipoprotein receptor-related protein-1 (LRP1) in APP/PS1 mice after electroacupuncture (EA) treatment and further to explore the mechanism. Methods. Forty 6-month-old APP/PS1 mice were randomly divided into a model group and an EA group, with twenty wild-type mice used as a normal control group. Mice in the EA group were treated with EA at GV 20 (băi huì) and bilateral KI 1 (yŏng quán) acupoints for 6 weeks. The Morris water maze was applied to assess the spatial memory in behavior...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27824728/evidence-that-ldl-receptor-related-protein-1-acts-as-an-early-injury-detection-receptor-and-activates-c-jun-in-schwann-cells
#7
Andreas Flütsch, Kenneth Henry, Elisabetta Mantuano, Michael S Lam, Masataka Shibayama, Kazuhisa Takahashi, Steven L Gonias, Wendy M Campana
Schwann cells (SCs) detect injury to peripheral nerves and transform phenotypically to respond to injury and facilitate repair. Cell-signaling pathways and changes in gene expression that drive SC phenotypic transformation in injury have been described; however, the SC receptors that detect peripheral nervous system (PNS) injury have not been identified. LDL receptor-related protein 1 (LRP1) is a receptor for numerous ligands, including intracellular proteins released by injured cells and protein components of degenerated myelin...
December 14, 2016: Neuroreport
https://www.readbyqxmd.com/read/27794518/evidence-that-factor-viii-forms-a-bivalent-complex-with-the-ldl-receptor-related-protein-1-lrp1-identification-of-cluster-iv-on-lrp1-as-the-major-binding-site
#8
Patricia A Young, Mary Migliorini, Dudley K Strickland
Hemophilia A is a bleeding disorder caused by a deficiency in coagulation factor VIII (fVIII) that affects 1 in 5,000 males. Current prophylactic replacement therapy, while effective, is difficult to maintain due to the cost and frequency of injections. Hepatic clearance of fVIII is mediated by the LDL receptor-related protein 1 (LRP1), a member of the LDL receptor family. While it is well established that fVIII binds LRP1, the molecular details of this interaction are unclear, as most of the studies have been performed using fragments of fVIII and LRP1...
October 29, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27732771/n-glycan-truncation-causes-enhanced-clearance-of-plasma-derived-von-willebrand-factor
#9
Jamie M O'Sullivan, Sonia Aguila, Emily McRae, Soracha E Ward, Orla Rawley, Padraic G Fallon, Teresa M Brophy, Roger J S Preston, Lauren Brady, Orla Sheils, Alain Chion, James S O'Donnell
BACKGROUND: Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD). In addition, previous studies have demonstrated that VWF glycans play a key role in regulating in vivo clearance. However, the molecular mechanisms underlying VWF clearance remain poorly understood. OBJECTIVE: To define the molecular mechanisms through which VWF N-glycan structures influence in vivo clearance. METHODS: Using a series of exoglycosidases, different pd-VWF glycoforms were generated...
October 12, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27701147/cancer-associated-fibroblast-derived-annexin-a6-extracellular-vesicles-support-pancreatic-cancer-aggressiveness
#10
Julie Leca, Sébastien Martinez, Sophie Lac, Jérémy Nigri, Véronique Secq, Marion Rubis, Christian Bressy, Arnauld Sergé, Marie-Noelle Lavaut, Nelson Dusetti, Céline Loncle, Julie Roques, Daniel Pietrasz, Corinne Bousquet, Stéphane Garcia, Samuel Granjeaud, Mehdi Ouaissi, Jean Baptiste Bachet, Christine Brun, Juan L Iovanna, Pascale Zimmermann, Sophie Vasseur, Richard Tomasini
The intratumoral microenvironment, or stroma, is of major importance in the pathobiology of pancreatic ductal adenocarcinoma (PDA), and specific conditions in the stroma may promote increased cancer aggressiveness. We hypothesized that this heterogeneous and evolving compartment drastically influences tumor cell abilities, which in turn influences PDA aggressiveness through crosstalk that is mediated by extracellular vesicles (EVs). Here, we have analyzed the PDA proteomic stromal signature and identified a contribution of the annexin A6/LDL receptor-related protein 1/thrombospondin 1 (ANXA6/LRP1/TSP1) complex in tumor cell crosstalk...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27698954/korean-pine-nut-oil-replacement-decreases-intestinal-lipid-uptake-while-improves-hepatic-lipid-metabolism-in-mice
#11
Shuang Zhu, Soyoung Park, Yeseo Lim, Sunhye Shin, Sung Nim Han
BACKGROUND/OBJECTIVES: Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS: Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks...
October 2016: Nutrition Research and Practice
https://www.readbyqxmd.com/read/27682851/presumed-lrp1-targeting-transport-peptide-delivers-%C3%AE-secretase-inhibitor-to-neurons-in-vitro-with-limited-efficiency
#12
Jong Ah Kim, Tommaso Casalini, Davide Brambilla, Jean-Christophe Leroux
Interfering with the activity of β-secretase to reduce the production of Aβ peptides is a conceivable therapeutic strategy for Alzheimer's disease. However, the development of efficient yet safe inhibitors is hampered by secondary effects, usually linked to the indiscriminate inhibition of other substrates' processing by the targeted enzyme. Based on the spatial compartmentalization of the cleavage of the amyloid precursor protein by β-secretase, we hypothesized that by exploiting the endocytosis receptor low-density lipoprotein receptor-related protein it would be possible to direct an otherwise cell-impermeable inhibitor to the endosomes of neurons, boosting the drug's efficacy and importantly, sparing the off-target effects...
September 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27680891/macrophages-of-genetically-characterized-familial-hypercholesterolaemia-patients-show-up-regulation-of-ldl-receptor-related-proteins
#13
Rafael Escate, Teresa Padro, Maria Borrell-Pages, Rosa Suades, Rosa Aledo, Pedro Mata, Lina Badimon
Familial hypercholesterolaemia (FH) is a major risk for premature coronary heart disease due to severe long-life exposure to high LDL levels. Accumulation of LDL in the vascular wall triggers atherosclerosis with activation of the innate immunity system. Here, we have investigated (i) gene expression of LDLR and LRPs in peripheral blood cells (PBLs) and in differentiated macrophages of young FH-patients; and (ii) whether macrophage from FH patients have a differential response when exposed to high levels of atherogenic LDL...
September 29, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27644406/rapid-hepatic-clearance-of-full-length-ccn-2-ctgf-a-putative-role-for-lrp1-mediated-endocytosis
#14
K G F Gerritsen, N Bovenschen, T Q Nguyen, D Sprengers, M P Koeners, A N van Koppen, J A Joles, R Goldschmeding, R J Kok
CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min)...
September 19, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27614059/lrp1-contributes-to-the-clearance-of-the-factor-viia-antithrombin-complex
#15
Judicael G Fazavana, Vincent Muczynski, Valerie Proulle, Nikolett Wohner, Olivier D Christophe, Peter J Lenting, Cécile V Denis
BACKGROUND: Recent findings point to activated factor VII (FVIIa) being cleared predominantly (±65% of the injected protein) as part of a complex with the serpin antithrombin. FVIIa/antithrombin complexes are targeted to hepatocytes and liver macrophages. Both cells lines abundantly express LRP1, a scavenger-receptor mediating clearance of protease/serpin complexes. OBJECTIVES: To investigate whether the FVIIa/antithrombin complex is a ligand for LRP1. METHODS: Binding of FVIIa and pre-formed FVIIa/antithrombin complexes to purified LRP1-fragment Cluster-IV (sLRP1-cIV/Fc) and to human & murine macrophages was analyzed...
September 10, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27582494/engineered-tissue-inhibitor-of-metalloproteinases-3-variants-resistant-to-endocytosis-have-prolonged-chondroprotective-activity
#16
Christine M Doherty, Robert Visse, Deendayal Dinakarpandian, Dudley K Strickland, Hideaki Nagase, Linda Troeberg
Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a central inhibitor of matrix-degrading and sheddase families of metalloproteinases. Extracellular levels of the inhibitor are regulated by the balance between its retention on the extracellular matrix and its endocytic clearance by the scavenger receptor low density lipoprotein receptor-related protein 1 (LRP1). Here, we used molecular modeling to predict TIMP-3 residues potentially involved in binding to LRP1 based on the proposed LRP1 binding motif of 2 lysine residues separated by about 21 Å and mutated the candidate lysine residues to alanine individually and in pairs...
October 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27569546/genetic-variants-in-lrp1-and-ulk4-are-associated-with-acute-aortic-dissections
#17
Dong-Chuan Guo, Megan L Grove, Siddharth K Prakash, Per Eriksson, Ellen M Hostetler, Scott A LeMaire, Simon C Body, Sherene Shalhub, Anthony L Estrera, Hazim J Safi, Ellen S Regalado, Wei Zhou, Michael R Mathis, Kim A Eagle, Bo Yang, Cristen J Willer, Eric Boerwinkle, Dianna M Milewicz
Acute aortic dissections are a preventable cause of sudden death if individuals at risk are identified and surgically repaired in a non-emergency setting. Although mutations in single genes can be used to identify at-risk individuals, the majority of dissection case subjects do not have evidence of a single gene disorder, but rather have the other major risk factor for dissections, hypertension. Initial genome-wide association studies (GWASs) identified SNPs at the FBN1 locus associated with both thoracic aortic aneurysms and dissections...
September 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27565578/the-activities-of-ldl-receptor-related-protein-1-lrp1-compartmentalize-into-distinct-plasma-membrane-microdomains
#18
Emilia Laudati, Andrew S Gilder, Michael S Lam, Roberta Misasi, Maurizio Sorice, Steven L Gonias, Elisabetta Mantuano
LDL Receptor-related Protein-1 (LRP1) is an endocytic receptor for diverse ligands. In neurons and neuron-like cells, ligand-binding to LRP1 initiates cell-signaling. Herein, we show that in PC12 and N2a neuron-like cells, LRP1 distributes into lipid rafts and non-raft plasma membrane fractions. When lipid rafts were disrupted, using methyl-β-cyclodextrin or fumonisin B1, activation of Src family kinases and ERK1/2 by the LRP1 ligands, tissue-type plasminogen activator and activated α2-macroglobulin, was blocked...
October 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27563375/hiv-1-tat-regulates-occludin-and-a%C3%AE-transfer-receptor-expression-in-brain-endothelial-cells-via-rho-rock-signaling-pathway
#19
Yanlan Chen, Wen Huang, Wenlin Jiang, Xianghong Wu, Biao Ye, Xiaoting Zhou
HIV-1 transactivator protein (Tat) has been shown to play an important role in HIV-associated neurocognitive disorders. The aim of the present study was to evaluate the relationship between occludin and amyloid-beta (Aβ) transfer receptors in human cerebral microvascular endothelial cells (hCMEC/D3) in the context of HIV-1-related pathology. The protein expressions of occludin, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in hCMEC/D3 cells were examined using western blotting and immunofluorescent staining...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27522265/the-p2y2-receptor-mediates-uptake-of-matrix-retained-and-aggregated-low-density-lipoprotein-in-primary-vascular-smooth-muscle-cells
#20
Tixieanna Dissmore, Cheikh I Seye, Denis M Medeiros, Gary A Weisman, Barry Bardford, Laman Mamedova
BACKGROUND AND AIMS: The internalization of aggregated low-density lipoproteins (agLDL) mediated by low-density lipoprotein receptor related protein (LRP1) may involve the actin cytoskeleton in ways that differ from the endocytosis of soluble LDL by the LDL receptor (LDLR). This study aims to define novel mechanisms of agLDL uptake through modulation of the actin cytoskeleton, to identify molecular targets involved in foam cell formation in vascular smooth muscle cells (VSMCs). The critical observation that formed the basis for these studies is that under pathophysiological conditions, nucleotide release from blood-derived and vascular cells activates SMC P2Y2 receptors (P2Y2Rs) leading to rearrangement of the actin cytoskeleton and cell motility...
September 2016: Atherosclerosis
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