Identification of Sortilin Alternatively Spliced Variants in Mouse 3T3L1
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Autism Multiplex Family with 16P11.2P12.2 Microduplication Syndrome in Monozygotic Twins and Distal 16P11.2 Deletion in Their Brother
European Journal of Human Genetics (2012) 20, 540–546 & 2012 Macmillan Publishers Limited All rights reserved 1018-4813/12 www.nature.com/ejhg ARTICLE Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother Anne-Claude Tabet1,2,3,4, Marion Pilorge2,3,4, Richard Delorme5,6,Fre´de´rique Amsellem5,6, Jean-Marc Pinard7, Marion Leboyer6,8,9, Alain Verloes10, Brigitte Benzacken1,11,12 and Catalina Betancur*,2,3,4 The pericentromeric region of chromosome 16p is rich in segmental duplications that predispose to rearrangements through non-allelic homologous recombination. Several recurrent copy number variations have been described recently in chromosome 16p. 16p11.2 rearrangements (29.5–30.1 Mb) are associated with autism, intellectual disability (ID) and other neurodevelopmental disorders. Another recognizable but less common microdeletion syndrome in 16p11.2p12.2 (21.4 to 28.5–30.1 Mb) has been described in six individuals with ID, whereas apparently reciprocal duplications, studied by standard cytogenetic and fluorescence in situ hybridization techniques, have been reported in three patients with autism spectrum disorders. Here, we report a multiplex family with three boys affected with autism, including two monozygotic twins carrying a de novo 16p11.2p12.2 duplication of 8.95 Mb (21.28–30.23 Mb) characterized by single-nucleotide polymorphism array, encompassing both the 16p11.2 and 16p11.2p12.2 regions. The twins exhibited autism, severe ID, and dysmorphic features, including a triangular face, deep-set eyes, large and prominent nasal bridge, and tall, slender build. The eldest brother presented with autism, mild ID, early-onset obesity and normal craniofacial features, and carried a smaller, overlapping 16p11.2 microdeletion of 847 kb (28.40–29.25 Mb), inherited from his apparently healthy father. -
Sortilin Expression Is Essential for Pro-Nerve Growth Factor-Induced Apoptosis of Rat Vascular Smooth Muscle Cells
Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells. Campagnolo, Luisa; Costanza, Gaetana; Francesconi, Arianna; Arcuri, Gaetano; Moscatelli, Ilana; Orlandi, Augusto Published in: PLoS ONE DOI: 10.1371/journal.pone.0084969 2014 Link to publication Citation for published version (APA): Campagnolo, L., Costanza, G., Francesconi, A., Arcuri, G., Moscatelli, I., & Orlandi, A. (2014). Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells. PLoS ONE, 9(1), [e84969]. https://doi.org/10.1371/journal.pone.0084969 Total number of authors: 6 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove -
Prongf Induces Tnfα-Dependent Death of Retinal Ganglion Cells Through a P75ntr Non-Cell-Autonomous Signaling Pathway
ProNGF induces TNFα-dependent death of retinal ganglion cells through a p75NTR non-cell-autonomous signaling pathway Frédéric Lebrun-Juliena,1, Mathieu J. Bertrandb,1, Olivier De Backerc, David Stellwagend, Carlos R. Moralese, Adriana Di Polo a,2,3, and Philip A. Barker b,2 aDepartment of Pathology and Cell Biology and Groupe de Recherche sur le Système Nerveux Central, Université de Montréal, Montreal, Quebec H3C 3J7, Canada; bCentre for Neuronal Survival, Montreal Neurological Institute, Montreal, Quebec H3A 2B4, Canada; cFacultés Universitaires Notre-Dame de la Paix School of Medicine, University of Namur, Namur B-5000, Belgium; dCentre for Research in Neuroscience, Montreal, Quebec H3G 1A4; and eDepartment of Anatomy and Cell Biology McGill University, Montreal, Quebec H3A 2B2, Canada Edited by Moses V. Chao, Skirball Institute of Biomolecular Medicine, New York, New York, and accepted by the Editorial Board December 30, 2009 (received for review August 17, 2009) Neurotrophin binding to the p75 neurotrophin receptor (p75NTR) Müller glial cells. Therefore, proNGF-induced neuronal loss in the activates neuronal apoptosis following adult central nervous sys- adult retina occurs through a non-cell-autonomous mechanism. tem injury, but the underlying cellular mechanisms remain poorly defined. In this study, we show that the proform of nerve growth Results factor (proNGF) induces death of retinal ganglion cells in adult ProNGF Induces Death of Retinal Ganglion Cells in Adult Rodents. To rodents via a p75NTR-dependent signaling mechanism. Expression investigate whether proNGF promotes neuronal death in vivo, we of p75NTR in the adult retina is confined to Müller glial cells; there- first retrogradely labeled RGCs of adult rats by applying fluo- fore we tested the hypothesis that proNGF activates a non-cell- rogold to the surface of the superior colliculus and then provided autonomous signaling pathway to induce retinal ganglion cell a single intraocular injection of proNGF or vehicle. -
The Cellular Nucleic Acid Binding Protein Regulates the Alzheimer’S Disease Β-Secretase Protein Bace1
University of Kentucky UKnowledge Theses and Dissertations--Molecular and Cellular Biochemistry Molecular and Cellular Biochemistry 2012 THE CELLULAR NUCLEIC ACID BINDING PROTEIN REGULATES THE ALZHEIMER’S DISEASE β-SECRETASE PROTEIN BACE1 Christopher J. Holler University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Holler, Christopher J., "THE CELLULAR NUCLEIC ACID BINDING PROTEIN REGULATES THE ALZHEIMER’S DISEASE β-SECRETASE PROTEIN BACE1" (2012). Theses and Dissertations--Molecular and Cellular Biochemistry. 12. https://uknowledge.uky.edu/biochem_etds/12 This Doctoral Dissertation is brought to you for free and open access by the Molecular and Cellular Biochemistry at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Molecular and Cellular Biochemistry by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained and attached hereto needed written permission statements(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine). I hereby grant to The University of Kentucky and its agents the non-exclusive license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. I agree that the document mentioned above may be made available immediately for worldwide access unless a preapproved embargo applies. -
BACE1 Function and Inhibition: Implications of Intervention in the Amyloid Pathway of Alzheimer’S Disease Pathology
Review BACE1 Function and Inhibition: Implications of Intervention in the Amyloid Pathway of Alzheimer’s Disease Pathology Gerald Koelsch CoMentis, Inc., South San Francisco, CA 94080, USA; [email protected] Received: 15 September 2017; Accepted: 10 October 2017; Published: 13 October 2017 Abstract: Alzheimer’s disease (AD) is a fatal progressive neurodegenerative disorder characterized by increasing loss in memory, cognition, and function of daily living. Among the many pathologic events observed in the progression of AD, changes in amyloid β peptide (Aβ) metabolism proceed fastest, and precede clinical symptoms. BACE1 (β-secretase 1) catalyzes the initial cleavage of the amyloid precursor protein to generate Aβ. Therefore inhibition of BACE1 activity could block one of the earliest pathologic events in AD. However, therapeutic BACE1 inhibition to block Aβ production may need to be balanced with possible effects that might result from diminished physiologic functions BACE1, in particular processing of substrates involved in neuronal function of the brain and periphery. Potentials for beneficial or consequential effects resulting from pharmacologic inhibition of BACE1 are reviewed in context of ongoing clinical trials testing the effect of BACE1 candidate inhibitor drugs in AD populations. Keywords: Alzheimer’s disease; amyloid hypothesis; BACE1; beta secretase; pharmacology 1. Introduction Alzheimer’s disease (AD) is a fatal progressive neurodegenerative disorder, slowly eroding memory, cognition, and functions of daily living, inevitably culminating in death from pneumonia and infectious diseases resulting from failure to thrive, loss of fine motor skills, and incapacitation. Treatment is limited to therapeutics that alleviate symptoms of memory loss, but are effective for a relatively short duration during and after which disease progression continues. -
NTR3/Sortilin [G11]: MC0188 Intended Use: for Research Use Only
Medaysis Enable Innovation DATA SHEET Mouse Anti-NTR3/Sortilin [G11]: MC0188 Intended Use: For Research Use Only Description: Neurotensin (NT) initiates an intracellular response by interacting with the G protein-coupled receptors NTR1 (NTS1 receptor, high affinity NTR) and NTR2 (NTS2 receptor, levocabastine-sensitive neurotensin receptor), and the type I receptor NTR3 (NTS3 receptor, sortilin-1, Gp95). NT has a wide distribution in regions of the brain and in peripheral tissues where NT receptors can contribute to hypotension, hyperglycemia, hypothermia, antinociception and regulation of intestinal motility and secretion. HL-60 cells express NTR1, which can couple to Gq, Gi/o, or Gs. Alternative splicing of rat NTR2 can generate a 5-transmembrane domain variant isoform that is co-expressed with the fulllength NTR2 throughout the brain and spinal cord. NTR3 activation in the murine microglial cell line N11 induces MIP-2, Specifications Clone: G11 Source: Mouse Isotype: IgG1k Reactivity: Human, mouse, rat Localization: Membrane, cytoplasm Formulation: Purified antibody in PBS pH7.4, containing BSA and ≤ 0.09% sodium azide (NaN3) Storage: Store at 2°- 8°C Applications: ELISA, IHC, IF, IP, WB Package: Description Catalog No. Size NTR3/Sortilin Concentrated MC0188 1 ml IHC Procedure* Positive Control Tissue: Brain Concentrated Dilution: 50-200 Pretreatment: Citrate pH6.0 or EDTA pH8.0, 15 minutes using Pressure Cooker, or 30-60 minutes using water bath at 95°-99°C Incubation Time and Temp: 30-60 minutes @ RT Detection: Refer to the detection system manual * Result should be confirmed by an established diagnostic procedure. FFPE human epididymis tissue stained with anti- NTR3/Sortilin using DAB References: 1. -
Rabbit Anti-RABEP1 Antibody-SL19721R
SunLong Biotech Co.,LTD Tel: 0086-571- 56623320 Fax:0086-571- 56623318 E-mail:[email protected] www.sunlongbiotech.com Rabbit Anti-RABEP1 antibody SL19721R Product Name: RABEP1 Chinese Name: RABEP1蛋白抗体 Neurocrescin; Rab GTPase binding effector protein 1; RAB5EP; Rabaptin 4; Rabaptin Alias: 5; Rabaptin 5alpha; RABPT5; RABPT5A; Renal carcinoma antigen NY REN 17; Renal carcinoma antigen NYREN17. Organism Species: Rabbit Clonality: Polyclonal React Species: Human,Mouse,Rat, ELISA=1:500-1000IHC-P=1:400-800IHC-F=1:400-800ICC=1:100-500IF=1:100- 500(Paraffin sections need antigen repair) Applications: not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user. Molecular weight: 99kDa Cellular localization: The cell membrane Form: Lyophilized or Liquid Concentration: 1mg/ml immunogen: KLH conjugated synthetic peptide derived from human RABEP1:501-600/862 Lsotype: IgGwww.sunlongbiotech.com Purification: affinity purified by Protein A Storage Buffer: 0.01M TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol. Store at -20 °C for one year. Avoid repeated freeze/thaw cycles. The lyophilized antibody is stable at room temperature for at least one month and for greater than a year Storage: when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C. PubMed: PubMed RABEP1 is a Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. It is involved in endocytic membrane fusion and membrane trafficking of Product Detail: recycling endosomes. Stimulates RABGEF1 mediated nucleotide exchange on RAB5A. -
Independent and Epistatic Effects of Variants in VPS10-D Receptors on Alzheimer Disease Risk and Processing of the Amyloid Precursor Protein (APP)
Citation: Transl Psychiatry (2013) 3, e256; doi:10.1038/tp.2013.13 & 2013 Macmillan Publishers Limited All rights reserved 2158-3188/13 www.nature.com/tp Independent and epistatic effects of variants in VPS10-d receptors on Alzheimer disease risk and processing of the amyloid precursor protein (APP) C Reitz1,2,3, G Tosto2, B Vardarajan4, E Rogaeva5, M Ghani5, RS Rogers2, C Conrad2, JL Haines6, MA Pericak-Vance7, MD Fallin8, T Foroud9, LA Farrer4,10,11,12,13,14, GD Schellenberg15, PS George-Hyslop5,16,17, R Mayeux1,2,3,18,19,20 and the Alzheimer’s Disease Genetics Consortium (ADGC) Genetic variants in the sortilin-related receptor (SORL1) and the sortilin-related vacuolar protein sorting 10 (VPS10) domain- containing receptor 1 (SORCS1) are associated with increased risk of Alzheimer’s disease (AD), declining cognitive function and altered amyloid precursor protein (APP) processing. We explored whether other members of the (VPS10) domain-containing receptor protein family (the sortilin-related VPS10 domain-containing receptors 2 and 3 (SORCS2 and SORCS3) and sortilin (SORT1)) would have similar effects either independently or together. We conducted the analyses in a large Caucasian case control data set (n ¼ 11 840 cases, 10 931 controls) to determine the associations between single nucleotide polymorphisms (SNPs) in all the five homologous genes and AD risk. Evidence for interactions between SNPs in the five VPS10 domain receptor family genes was determined in epistatic statistical models. We also compared expression levels of SORCS2, SORCS3 and SORT1 in AD and control brains using microarray gene expression analyses and assessed the effects of these genes on c-secretase processing of APP. -
Apolipoprotein(A) Secretion Is Modulated by Sortilin, Proprotein Convertase Subtilisin/Kexin Type 9, and Microsomal Triglyceride Transfer Protein
Western University Scholarship@Western Electronic Thesis and Dissertation Repository 6-24-2019 10:30 AM Apolipoprotein(a) Secretion is Modulated by Sortilin, Proprotein Convertase Subtilisin/Kexin Type 9, and Microsomal Triglyceride Transfer Protein Justin Clark The University of Western Ontario Supervisor Koschinsky, Marlys L. Robarts Research Institute Graduate Program in Physiology and Pharmacology A thesis submitted in partial fulfillment of the equirr ements for the degree in Master of Science © Justin Clark 2019 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Cardiovascular Diseases Commons Recommended Citation Clark, Justin, "Apolipoprotein(a) Secretion is Modulated by Sortilin, Proprotein Convertase Subtilisin/Kexin Type 9, and Microsomal Triglyceride Transfer Protein" (2019). Electronic Thesis and Dissertation Repository. 6310. https://ir.lib.uwo.ca/etd/6310 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. Abstract Elevated plasma lipoprotein(a) (Lp(a)) levels are a causal risk factor for cardiovascular disease (CVD), but development of specific Lp(a) lowering therapeutics has been hindered by insufficient understanding of Lp(a) biology. For example, the location of the noncovalent interaction that precedes the extracellular disulfide linkage between apolipoprotein(a) (apo(a)) and apolipoprotein B-100 (apoB-100) in Lp(a) biosynthesis is unclear. In this study we modulated known intracellular regulators of apoB-100 production and then assessed apo(a) secretion from human HepG2 cells expressing 17-kringle (17K) apo(a) isoform variants using pulse-chase analysis. -
Effect of Alzheimer's Disease Risk Variant Rs3824968 at SORL1 On
www.nature.com/scientificreports OPEN Effect of Alzheimer's Disease Risk Variant rs3824968 at SORL1 on Regional Gray Matter Volume and Received: 30 November 2015 Accepted: 01 March 2016 Age-Related Interaction in Adult Published: 21 March 2016 Lifespan Chu-Chung Huang1,6, Mu-En Liu2,3,4, Hung-Wen Kao5,8, Kun-Hsien Chou6, Albert C. Yang2,4,7, Ying-Hsiu Wang2, Tong-Ru Chen2, Shih-Jen Tsai2,4 & Ching-Po Lin1,6,8 Sortilin receptor 1 (SORL1) is involved in cellular trafficking of amyloid precursor protein and plays an essential role in amyloid-beta peptide generation in Alzheimer disease (AD). The major A allele in a SORL1 single nucleotide polymorphism (SNP), rs3824968, is associated with an increased AD risk. However, the role of SORL1 rs3824968 in the normal ageing process has rarely been examined in relation to brain structural morphology. This study investigated the association between SORL1 rs3824968 and grey matter (GM) volume in a nondemented Chinese population of 318 adults within a wide age range (21–92 years). Through voxel-based morphometry, we found that participants carrying SORL1 allele A exhibited significantly smaller GM volumes in the right posterior cingulate, left middle occipital, medial frontal, and superior temporal gyri. Considerable interaction between age and SORL1 suggested a detrimental and accelerated ageing effect of allele A on putamen. These findings provide evidence that SORL1 rs3824968 modulates regional GM volume and is associated with brain trajectory during the adult lifespan. The sortilin-related receptor gene (SORL1) encodes a mosaic protein belonging to at least two families: the vac- uolar protein sorting 10 domain-containing receptor family and the low density lipoprotein receptor family. -
AAV-Mediated Progranulin Delivery to a Mouse Model of Progranulin Deficiency Causes T
bioRxiv preprint doi: https://doi.org/10.1101/308692; this version posted April 27, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. AAV-mediated progranulin delivery to a mouse model of progranulin deficiency causes T cell-mediated hippocampal degeneration by Defne A. Amado,1* Julianne M. Rieders,2* Fortunay Diatta,1 Pilar Hernandez-Con,1 Adina Singer,1 Junxian Zhang,1 Eric Lancaster,1 Beverly L. Davidson,2# and Alice S. Chen-Plotkin1# Affiliations 1. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA 19104 2. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA USA 19104; Children’s Hospital of Philadelphia, Philadelphia, PA USA 19104 *co-first authors #Co-corresponding authors: Beverly L. Davidson, PhD Children’s Hospital of Philadelphia 3501 Civic Center Boulevard, 5060 CTRB Philadelphia, PA 19104 Tel: 267-426-0929 Email: [email protected] Alice S. Chen-Plotkin, MD 3 W Gates Department of Neurology 3400 Spruce Street Philadelphia, PA 19104 USA Tel: 215-573-7193 Email: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/308692; this version posted April 27, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Adeno-associated virus (AAV)-mediated gene replacement is emerging as a safe and effective means of correcting single-gene mutations, and use of AAV vectors for treatment of diseases of the CNS is increasing. -
Parkinson's Disease-Linked D620N VPS35 Knockin Mice
Parkinson’s disease-linked D620N VPS35 knockin mice manifest tau neuropathology and dopaminergic neurodegeneration Xi Chena, Jennifer K. Kordicha, Erin T. Williamsa, Nathan Levinea, Allyson Cole-Straussb, Lee Marshalla, Viviane Labriea,c, Jiyan Maa, Jack W. Liptonb, and Darren J. Moorea,1 aCenter for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503; bDepartment of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI 49503; and cDivision of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 Edited by Anders Björklund, Lund University, Lund, Sweden, and approved February 13, 2019 (received for review August 30, 2018) Mutations in the vacuolar protein sorting 35 ortholog (VPS35) since only a single D620N mutation carrier has been evaluated at gene represent a cause of late-onset, autosomal dominant familial autopsy but with the notable exception of key PD-relevant brain Parkinson’s disease (PD). A single missense mutation, D620N, is regions (i.e., substantia nigra, locus ceruleus, or any brainstem considered pathogenic based upon its segregation with disease area) (7). Outside of these areas, VPS35 mutation carriers lack in multiple families with PD. At present, the mechanism(s) by extranigral α-synuclein–positive Lewy body pathology (7), a which familial VPS35 mutations precipitate neurodegeneration in characteristic hallmark of PD brains. The mechanism by which PD are poorly understood. Here, we employ a germline D620N dominantly inherited mutations in VPS35 induce neuropathology VPS35 knockin (KI) mouse model of PD to formally establish the and neurodegeneration in PD remains enigmatic. age-related pathogenic effects of the D620N mutation at physiolog- VPS35 encodes a core component of the retromer complex, ical expression levels.