DOCSLIB.ORG

Chromogranin a Dependent Upon Interaction with Biogenesis in Mast

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chromogranin a Dependent Upon Interaction with Biogenesis in Mast Secretogranin III Directs Secretory Vesicle Biogenesis in Mast Cells in a Manner Dependent upon Interaction with Chromogranin A This information is current as of October 4, 2021. Prerna Prasad, Angel A. Yanagihara, Andrea L. Small-Howard, Helen Turner and Alexander J. Stokes J Immunol 2008; 181:5024-5034; ; doi: 10.4049/jimmunol.181.7.5024 http://www.jimmunol.org/content/181/7/5024 Downloaded from References This article cites 42 articles, 15 of which you can access for free at: http://www.jimmunol.org/content/181/7/5024.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on October 4, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Secretogranin III Directs Secretory Vesicle Biogenesis in Mast Cells in a Manner Dependent upon Interaction with Chromogranin A1 Prerna Prasad,2*§ Angel A. Yanagihara,2‡ Andrea L. Small-Howard,2* Helen Turner,2,3*† and Alexander J. Stokes2*†¶ Mast cells are granular immunocytes that reside in the body’s barrier tissues. These cells orchestrate inflammatory responses. Proinflammatory mediators are stored in granular structures within the mast cell cytosol. Control of mast cell granule exocytosis is a major therapeutic goal for allergic and inflammatory diseases. However, the proteins that control granule biogenesis and abundance in mast cells have not been elucidated. In neuroendocrine cells, whose dense core granules are strikingly similar to mast cell granules, granin proteins regulate granulogenesis. Our studies suggest that the Secretogranin III (SgIII) protein is involved in secretory granule biogenesis in mast cells. SgIII is abundant in mast cells, and is organized into vesicular structures. Our results Downloaded from show that over-expression of SgIII in mast cells is sufficient to cause an expansion of a granular compartment in these cells. These novel granules store inflammatory mediators that are released in response to physiological stimuli, indicating that they function as bona fide secretory vesicles. In mast cells, as in neuroendocrine cells, we show that SgIII is complexed with Chromogranin A (CgA). CgA is granulogenic when complexed with SgIII. Our data show that a novel non-granulogenic truncation mutant of SgIII (1–210) lacks the ability to interact with CgA. Thus, in mast cells, a CgA-SgIII complex may play a key role in secretory granule biogenesis. SgIII function in mast cells is unlikely to be limited to its partnership with CgA, as our interaction trap analysis http://www.jimmunol.org/ suggests that SgIII has multiple binding partners, including the mast cell ion channel TRPA1. The Journal of Immunology, 2008, 181: 5024–5034. he granin family (Chromogranin A (CgA),4 Chromo- pacity, low affinity, calcium binding proteins that are closely as- granin B (CgB), Secretogranin (Sg) II, and the less well sociated with calcium-regulated intracellular ion channels T studied Secretogranins III-VII) comprises a group of (10–13). Moreover, emerging evidence suggests that these pro- acidic proteins that are present in the secretory granules of a wide teins play an active role in directing the biosynthesis of secretory variety of endocrine and neuro-endocrine cells (1–4). The molec- granules. This biological role for granins has been proposed on the by guest on October 4, 2021 ular functions of the granins are poorly understood. There is evi- basis of work in neuroendocrine cells, where several granin pro- dence that granins may be the precursors of biologically active teins are expressed and have been shown to cooperatively contrib- peptides (3, 5–9). However, granins cannot be considered simply ute to secretory vesicle biogenesis (14, 15). This cooperation is as precursors of granule cargo. They may act as helper proteins in exemplified by the interaction between SgIII and CgA (15, 16). In the packaging of peptide hormones and neuro-peptides (3, 5–9). this study, an intermolecular interaction between the two granins is The EF-hand containing CgA and CgB may also act as high ca- needed for their targeting to secretory granules. Courel and coau- thors (15) have described a “granulogenic domain” in CgA that promotes the biogenesis of secretory granules probably through *Center for Biomedical Research at The Queen’s Medical Center, Honolulu, HI 96813; †Department of Cell and Molecular Biology, John A. Burns School of Med- exerting control over cholesterol sequestration and the dynamics of icine, University of Hawaii, Honolulu, HI 96813; ‡Pacific Bioscience Research Cen- intracellular vesicle budding/fusion. The potential contribution of ter, University of Hawaii, Honolulu, HI 96922; §Graduate Program in Microbiology, University of Hawaii, Honolulu, HI 96822; and ¶Program in Molecular Biosciences granins to the granularity of secretory immunocytes has not been and Bioengineering, University of Hawaii, Honolulu, HI 96822 addressed. Received for publication April 26, 2007. Accepted for publication July 23, 2008. Mast cells are densely granular, secretory leukocytes that reside The costs of publication of this article were defrayed in part by the payment of page in tissues (17, 18). In response to a variety of stimuli, including charges. This article must therefore be hereby marked advertisement in accordance immunological challenge, exposure to secretagogues and exposure with 18 U.S.C. Section 1734 solely to indicate this fact. to physical stimuli, mast cells release preformed, and de novo syn- 1 This work was supported by the Leahi Fund for Pulmonary Research (awards to thesized, inflammatory mediators into their surrounding tissues. H.T. and A.J.S.), McKee Fund (to A.J.S.), NIH RO1 GM 070634 (to H.T.) and NCRR INBRE P20RR016467 (sub-award to H.T.). The preformed mediators are housed within membrane-delimited 2 Current affiliations: H.T., Chaminade University of Honolulu; A.J.S., Center for secretory granules. The contents of mast cell secretory granules Cardiovascular Research, John. A. Burns School of Medicine, University of Hawaii; include inflammatory mediators such as histamine, serotonin, P.P., Institute for Biogenesis Research, John. A. Burns School of Medicine, Univer- ␣ sity of Hawaii; A. S.-H., AMDL, Tustin, CA. platelet activating factor, some cytokines (TNF- ), and matrix- 3 Address correspondence and reprint requests to Dr. Helen Turner, Castle Science active proteases of the chymase and tryptase families (17, 18). Center 116, Chaminade University, 3140 Waialae Avenue, Honolulu HI 96816. Together, these mediators exert diverse proinflammatory effects E-mail address: [email protected] or [email protected] upon tissue. These include the promotion of vasodilation, induc- 4 Abbreviations used in this paper: CgA, chromogranin A; CgB, chromogranin B; Sg, tion of inflammatory pain, and recruitment of other immunocytes secretogranin; w/v, weight-to-volume ratio; RT, room temperature. to the inflammatory site. The central role of these granules in in- Copyright © 2008 by The American Association of Immunologists, Inc. 0022-1767/08/$2.00 flammation has led to an intense interest in the signaling www.jimmunol.org The Journal of Immunology 5025 mechanisms that control granule exocytosis, because targets for anti- For production of TRex HEK293 cells with inducible expression of inflammatory therapeutics could lie within this system. Moreover, the SgIII constructs, parental cells were electroporated with 15 ␮g of plasmid ␮ mechanisms that control the biogenesis and abundance of these gran- DNA in a 500 l volume of DMEM/10% FBS/2 mM glutamine. Electro- porations were performed at 280 V/950 ␮F in a 4-mm path length cuvette ules are also of therapeutic interest, but remain poorly studied. (BioRad). Clonal cell lines were selected by limiting dilution in 400 ␮g/ml Mast cell granules are structurally, and functionally, related to zeocin and 5 ␮g/ml blasticidin, and screened by immunoprecipitation and the dense core vesicles of neuro-endocrine cells and neurons. Western blot. Transfected gene expression was induced using 1 ␮g/ml There has been no published analysis of the expression, or func- tetracycline for 16 h at 37°C. Whenever stable cell lines were produced, steps were taken to avoid the tion, of granins in the mast cell system, although their involvement possibility that experiments would be performed on progeny cells derived in secretory vesicle biogenesis in other neuroendocrine cells and from an original parental clone. After electroporation, a brief (12–14 h) neurons has been established (6, 7, 14, 19–23). In the current re- recovery period for the cells was used such that no discernable cell division port, we tested the idea that SgIII drives the production of mast cell took place. Recovered cells were trypsinized to a single cell suspension to secretory granules. Moreover, we propose that its interaction with disperse any potential daughter cell pairs. The trypsinized cell suspension was subjected to a limiting dilution (plated in a 96-well plate at less than CgA is critical to this biological role. Although SgIII and CgA one cell per well, (i.e., 0.5 cells per 250 ␮l medium)). Each well is there- proteins are abundant in various mast cells, we show that SgIII is fore unlikely to have more than one cell, but of course across the 960 wells depleted from the cytosol after stimulation of mast cells via either plated there will occasionally be wells where more than one cell is dis- pharmacological or immunological methods.
Load more

Recommended publications
  • Uncorrected Author Proof Boller Et Al
    Journal of Parkinson’s Disease xx (2020) x–xx 1 DOI 10.3233/JPD-202323 IOS Press 1 Review 2 Neuropathological and Biomarker Findings 3 in Parkinson’s Disease and Alzheimer’s 4 Disease: From Protein Aggregates to 5 Synaptic Dysfunction a,b,∗ c,d,e,∗ 6 Yaroslau Compta and Tamas Revesz a 7 Parkinson’s disease & Movement Disorders Unit, Neurology Service, Hospital Cl´ınic / IDIBAPS / CIBERNED, 8 Barcelona, Catalonia, Spain b 9 Institut de Neuroci`encies, Maextu’s excellence center, University of Barcelona, Barcelona, Catalonia, Spain c 10 Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, 11 UCL Queen Square Institute of Neurology, University College London, UK d 12 Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK 13 eDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College 14 London, UK Accepted 9 November 2020 15 Abstract. 16 There is mounting evidence that Parkinson’s disease (PD) and Alzheimer’s disease (AD) share neuropathological hallmarks, 17 while similar types of biomarkers are being applied to both. In this review we aimed to explore similarities and differences 18 between PD and AD at both the neuropathology and the biomarker levels, specifically focusing on protein aggregates 19 and synapse dysfunction. Thus, amyloid-␤ peptide (A␤) and tau lesions of the Alzheimer-type are common in PD and 20 ␣-synuclein Lewy-type aggregates are frequent findings in AD. Modern neuropathological techniques adding to routine 21 immunohistochemistry might take further our knowledge of these diseases beyond protein aggregates and down to their 22 presynaptic and postsynaptic terminals, with potential mechanistic and even future therapeutic implications.
    [Show full text]
  • Limited Diagnostic Utility of Chromogranin a Measurements in Workup of Neuroendocrine Tumors
    diagnostics Article Limited Diagnostic Utility of Chromogranin A Measurements in Workup of Neuroendocrine Tumors Jonas Baekdal 1,2,*, Jesper Krogh 1,2, Marianne Klose 1,2, Pernille Holmager 1,2, Seppo W. Langer 1,3, Peter Oturai 1,4,5, Andreas Kjaer 1,4,5 , Birgitte Federspiel 1,6, Linda Hilsted 1,7, Jens F. Rehfeld 1,7, Ulrich Knigge 1,2,8 and Mikkel Andreassen 1,2 1 ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark; [email protected] (J.K.); [email protected] (M.K.); [email protected] (P.H.); [email protected] (S.W.L.); [email protected] (P.O.); [email protected] (A.K.); [email protected] (B.F.); [email protected] (L.H.); [email protected] (J.F.R.); [email protected] (U.K.); [email protected] (M.A.) 2 Department of Endocrinology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 3 Department of Oncology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 4 Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Copenhagen University Hospital, 2100 Copenhagen, Denmark 5 Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, 2100 Copenhagen, Denmark 6 Department of Pathology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 7 Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 8 Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark * Correspondence: [email protected]; Tel.: +45-6013-4687 Received: 11 October 2020; Accepted: 28 October 2020; Published: 29 October 2020 Abstract: Background: Plasma chromogranin A (CgA) is related to tumor burden and recommended in the follow-up of patients diagnosed with neuroendocrine tumors (NETs).
    [Show full text]
  • Identification of VGF Nerve Growth Factor Inducible-Producing Cells In
    Int. J. Med. Sci. 2020, Vol. 17 480 Ivyspring International Publisher International Journal of Medical Sciences 2020; 17(4): 480-489. doi: 10.7150/ijms.39101 Research Paper Identification of VGF nerve growth factor inducible-producing cells in human spinal cords and expression change in patients with amyotrophic lateral sclerosis Yasuhiro Noda1, Miruto Tanaka1, Shinsuke Nakamura1, Junko Ito2, Akiyoshi Kakita2, Hideaki Hara1, and Masamitsu Shimazawa1 1. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. 2. Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan. Corresponding author: Dr. Masamitsu Shimazawa, Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. E-mail: [email protected], Telephone and Fax: +81-58-230-8126 © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2019.08.06; Accepted: 2019.12.23; Published: 2020.02.04 Abstract Amyotrophic lateral sclerosis (ALS) is a serious disease characterized by the degeneration of motor neurons resulting in muscle weakness and paralysis. The neuroendocrine polypeptide VGF is localized in the central nervous system and peripheral endocrine neurons and is cleaved into several polypeptides with multiple functions. Previous studies revealed that VGF was decreased in the cerebrospinal fluid of ALS model mice and sporadic ALS patients. However, it is unknown which cells supply VGF in the spinal cord and a detailed localization is lacking.
    [Show full text]
  • The Chromogranin A-Derived Peptides Catestatin and Vasostatin in Dogs
    Höglund et al. Acta Vet Scand (2020) 62:43 https://doi.org/10.1186/s13028-020-00541-3 Acta Veterinaria Scandinavica RESEARCH Open Access The chromogranin A-derived peptides catestatin and vasostatin in dogs with myxomatous mitral valve disease Katja Höglund1* , Jens Häggström2 , Odd Viking Höglund2 , Mats Stridsberg3 , Anna Tidholm2,4 and Ingrid Ljungvall2 Abstract Background: The protein chromogranin A (CgA) is stored and co-released with catecholamines from the stimulated adrenal glands. Increased plasma concentrations of CgA have been shown in people with heart disease. The aim of the study was to investigate whether plasma concentrations of the CgA-derived biologically active peptides catesta- tin and vasostatin were associated with the severity of myxomatous mitral valve disease (MMVD) in dogs and to assess potential associations between these blood variables and dog characteristics, echocardiographic variables, heart rate (HR), blood pressure (BP) and plasma N-terminal-proBNP (NT-proBNP) concentration. Sixty-seven privately owned dogs with or without MMVD were included. The dogs underwent physical examination, blood pressure measurement, blood sample collection, and echocardiographic examination. Plasma concentrations of catestatin and vasostatin were analyzed using radioimmunoassay. Results: Catestatin concentration decreased with increasing left atrial and ventricular size (R 2 0.09, P 0.019), and increased with increasing systolic and diastolic blood pressures (R2 0.08, P 0.038). Regression≤ analyses≤ showed no signifcant associations for vasostatin. No diferences in plasma concentrations≤ ≤ of catestatin or vasostatin were found between the disease severity groups used in the study. Conclusions: In the present dog population, the catestatin concentration showed weak negative associations with left atrial and ventricular sizes, both of which are known to increase with increasing severity of MMVD.
    [Show full text]
  • The Granin Protein Family in Cardiac Disease
    The granin protein family in cardiac disease Helge R. Røsjø, MD1,2,3 1 Division of Medicine, Akershus University Hospital, Lørenskog, Norway 2 Institute of Experimental Medical Research, Oslo University Hospital, Ullevål, Oslo, Norway 3 Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway © Helge R. Røsjø, 2012 Series of dissertations submitted to the Faculty of Medicine, University of Oslo No. 1333 ISBN 978-82-8264-359-7 All rights reserved. No part of this publication may be reproduced or transmitted, in any form or by any means, without permission. Cover: Inger Sandved Anfinsen. Printed in Norway: AIT Oslo AS. Produced in co-operation with Unipub. The thesis is produced by Unipub merely in connection with the thesis defence. Kindly direct all inquiries regarding the thesis to the copyright holder or the unit which grants the doctorate. Contents Supported by ......................................................................................................................... 4 Acknowledgments ................................................................................................................ 5 Abbreviations ........................................................................................................................ 8 List of papers in thesis: ....................................................................................................... 10 Introduction .......................................................................................................................
    [Show full text]
  • 030320 the Chromogranin–Secretogranin Family
    The new england journal of medicine review article mechanisms of disease The Chromogranin–Secretogranin Family Laurent Taupenot, Ph.D., Kimberly L. Harper, M.D., and Daniel T. O’Connor, M.D. From the Department of Medicine (L.T., eurons and neuroendocrine cells contain membrane- K.L.H., D.T.O.) and the Center for Molecular delimited pools of peptide hormones, biogenic amines, and neurotransmit- Genetics (D.T.O.), University of California n at San Diego, La Jolla; and the Veterans ters with a characteristic electron-dense appearance on transmission electron Affairs San Diego Healthcare System, San microscopy (Fig. 1). These vesicles, which are present throughout the neuroendocrine Diego, Calif. (L.T., K.L.H., D.T.O.). Address system1,2 and in a variety of neurons, store and release chromogranins and secretogranins reprint requests to Dr. O’Connor at the 3,4 Department of Medicine (9111H), Univer- (also known as “granins”), a unique group of acidic, soluble secretory proteins. The sity of California at San Diego, 3350 La Jolla three “classic” granins are chromogranin A, which was first isolated from chromaffin Village Dr., San Diego, CA 92161, or at cells of the adrenal medulla5,6; chromogranin B, initially characterized in a rat pheochro- [email protected]. mocytoma cell line7; and secretogranin II (sometimes called chromogranin C), which 8,9 N Engl J Med 2003;348:1134-49. was originally described in the anterior pituitary. Four other acidic secretory pro- Copyright © 2003 Massachusetts Medical Society. teins were later proposed for membership in the granin family10: secretogranin III (or 1B1075),11 secretogranin IV (or HISL-19),12 secretogranin V (or 7B2),13 and secretogra- nin VI (or NESP55).14 In this article, we review aspects of the structures, biochemical properties, and clin- ical importance of granins, with particular emphasis on chromogranin A, the granin that was discovered first and that has been studied most extensively.
    [Show full text]
  • Ganglioneurofibroma Arising Within the Extralobar Pulmonary Sequestration Yuanyuan Liu1, Wenbin Wu2, Longbo Gong2 and Miao Zhang2*
    Liu et al. Journal of Cardiothoracic Surgery (2020) 15:252 https://doi.org/10.1186/s13019-020-01295-9 CASE REPORT Open Access Ganglioneurofibroma arising within the extralobar pulmonary sequestration Yuanyuan Liu1, Wenbin Wu2, Longbo Gong2 and Miao Zhang2* Abstract Background: Neurogenic tumor arising within the pulmonary sequestration (PS) is rare. Case presentation: A 42-year-old asymptomatic female was referred to our hospital for work-up of extralobar PS. The independent feeding artery from the thoracic aorta was confirmed by three-dimensional computed tomography angiography (3D-CTA). Uniportal thoracoscopic resection of the sequestrated lung with mediastinal lymph node sampling was performed successfully. Ganglioneurofibroma within the PS was diagnosed as the specimen revealed positive expression of SRY-related HMG-box 10 protein, neuron-specific enolase, S-100, chromogranin A and synuclein. Tumor recurrence was not recorded 1 year after the surgery. Conclusion: Preoperative 3D-CTA is useful to identify the aberrant vessels of PS. An elaborate diagnostic work-up after a timely resection is necessary for subsequent management and follow-up plan. Keywords: Pulmonary sequestration (PS), Three-dimensional computed tomography angiography (3D-CTA), Uniportal, Single port, Video-assisted thoracoscopic surgery (VATS) Background Case presentation Ganglioneuroma is a rare, benign and well-differentiated This report was approved by the Institutional Review neurogenic tumor, which is mostly localized in the pos- Board of Xuzhou Central Hospital, and written informed terior mediastinum [1]. It usually grows very slow and consent was obtained from the patient. The clinical data displaces the surrounding anatomical structures without was presented anonymously for privacy concern. A 42- infiltration [2].
    [Show full text]
  • 1 1 2 3 Cell Type-Specific Transcriptomics of Hypothalamic
    1 2 3 4 Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to 5 weight-loss 6 7 Fredrick E. Henry1,†, Ken Sugino1,†, Adam Tozer2, Tiago Branco2, Scott M. Sternson1,* 8 9 1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 10 20147, USA. 11 2Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, 12 Cambridge CB2 0QH, UK 13 14 †Co-first author 15 *Correspondence to: [email protected] 16 Phone: 571-209-4103 17 18 Authors have no competing interests 19 1 20 Abstract 21 Molecular and cellular processes in neurons are critical for sensing and responding to energy 22 deficit states, such as during weight-loss. AGRP neurons are a key hypothalamic population 23 that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific 24 transcriptomics can be used to identify pathways that counteract weight-loss, and here we 25 report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived 26 young adult mice. For comparison, we also analyzed POMC neurons, an intermingled 27 population that suppresses appetite and body weight. We find that AGRP neurons are 28 considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell 29 type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion 30 channels, neuropeptides, and receptors. Combined with methods to validate and manipulate 31 these pathways, this resource greatly expands molecular insight into neuronal regulation of 32 body weight, and may be useful for devising therapeutic strategies for obesity and eating 33 disorders.
    [Show full text]
  • The Neural Chaperone Prosaas Blocks Α-Synuclein Fibrillation and Neurotoxicity
    The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity Timothy S. Jarvelaa, Hoa A. Lamb, Michael Helwiga,1, Nikolai Lorenzenc,2, Daniel E. Otzenc, Pamela J. McLeand, Nigel T. Maidmentb, and Iris Lindberga,3 aSchool of Medicine, University of Maryland, Baltimore, MD 21201; bDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90024; cInterdisciplinary Nanoscience Centre (iNANO), Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark; and dDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224 Edited by Solomon H. Snyder, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved June 14, 2016 (received for review January 20, 2016) Emerging evidence strongly suggests that chaperone proteins are the proprotein convertase PC1/3 (23, 24), proSAAS distribution cytoprotective in neurodegenerative proteinopathies involving pro- within the brain is far wider than that of PC1/3 (20, 21). ProSAAS tein aggregation; for example, in the accumulation of aggregated and PC1/3 expression are also not coregulated (25, 26), supporting a α-synuclein into the Lewy bodies present in Parkinson’sdisease.Of broader array of neuronal functions for proSAAS beyond its in- the various chaperones known to be associated with neurodegener- teractionwithPC1/3. ative disease, the small secretory chaperone known as proSAAS Interestingly, the proSAAS protein has been increasingly asso- (named after four residues in the amino terminal region) has many ciated with the presence of neurodegenerative disease. Immuno- attractive properties. We show here that proSAAS, widely expressed reactive proSAAS has been identified in neurofibrillary tangles in neurons throughout the brain, is associated with aggregated syn- and plaques in brain tissue from patients with Alzheimer’sdisease, uclein deposits in the substantia nigra of patients with Parkinson’s Pick’s disease, and Parkinsonism–dementia complex (27, 28).
    [Show full text]
  • Carboxypeptidase E Cytoplasmic Tail Mediates Localization of Synaptic
    JOURNAL OF NEUROCHEMISTRY | 2010 | 114 | 886–896 doi: 10.1111/j.1471-4159.2010.06820.x ,1 , ,1 *Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA Department of Neurosciences, University of Toledo, School of Medicine, Toledo, Ohio, USA àDepartment of Pharmacology, University of Michigan, School of Medicine, Ann Arbor, Michigan, USA Abstract tion. Yeast two-hybrid and pull-down experiments showed that How synaptic vesicles (SVs) are localized to the pre-active the CPE cytoplasmic tail interacted with c-adducin, which zone (5–200 nm beneath the active zone) in the nerve ter- binds actin enriched at the nerve terminal. Total internal minal, which may represent the slow response SV pool, is not reflective fluorescence (TIRF) microscopy using PC12 cells as fully understood. Electron microscopy revealed the number of a model showed that expression of GFP-CPEC15 reduced the SVs located in the pre-active zone, was significantly de- steady-state level of synaptophysin-mRFP containing synap- creased in hypothalamic neurons of carboxypeptidase E tic-like microvesicles accumulated in the area within 200 nm knockout (CPE-KO) mice compared with wild-type mice. from the sub-plasma membrane (TIRF zone). Our findings Additionally, we found K+-stimulated glutamate secretion from identify the CPE cytoplasmic tail, as a new mediator for the hypothalamic embryonic neurons was impaired in CPE-KO localization of SVs in the actin-rich pre-active zone in hypo- mice. Biochemical studies indicate that SVs from the hypo- thalamic neurons and the TIRF zone of PC12 cells.
    [Show full text]
  • The VGF-Derived Peptide TLQP-62 Modulates Insulin Secretion and Glucose Homeostasis
    P PETROCCHI-PASSERI and others Action of VGF peptides on 54:3 227–239 Research insulinoma cells The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis Pamela Petrocchi-Passeri1,2, Cheryl Cero3, Alessandro Cutarelli1,4, Claudio Frank4, Cinzia Severini2,5, Alessandro Bartolomucci3 and Roberta Possenti1,2 1Department of Medicine of Systems, University of Rome Tor Vergata, Via Montpellier, 100133 Rome, Italy Correspondence 2Institute of Cell Biology and Neurobiology, CNR, Rome, Italy should be addressed 3Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota, USA to R Possenti 4Istituto Superiore di Sanita` , Rome, Italy Email 5EBRI Foundation, Rome, Italy [email protected] Abstract Insulin secretion control is critical for glucose homeostasis. Paracrine and autocrine Key Words molecules secreted by cells of the islet of Langerhans, as well as by intramural and autonomic " neuropeptide neurons, control the release of different hormones that modulate insulin secretion. " intracellular calcium In pancreatic islets, the abundant presence of the granin protein VGF (nonacronymic; " signaling unrelated to VEGF) suggests that some of its proteolytically derived peptides could modulate " GSIS hormone release. Thus, in the present study, we screened several VGF-derived peptides for " diabetes their ability to induce insulin secretion, and we identified the VGF C-terminal peptide TLQP- 62 as the most effective fragment. TLQP-62 induced a potent increase in basal insulin secretion as well as in glucose-stimulated insulin secretion in several insulinoma cell lines. We Journal of Molecular Endocrinology found that this peptide stimulated insulin release via increased intracellular calcium mobilization and fast expression of the insulin 1 gene.
    [Show full text]
  • For Parkinson's Disease with Cognitive Impairment
    bioRxiv preprint doi: https://doi.org/10.1101/2021.03.19.436097; this version posted March 19, 2021. 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. Fibrinogen and Complement Factor H are promising CSF protein biomarker(s) for Parkinson’s disease with cognitive impairment- A Proteomics and ELISA based study Aditi Naskar1a, Albert Stezin2a, Arpitha Dharmappa3a, Shantala Hegde3a, Mariamma Philip4a, Nitish Kamble6a, Jitender Saini5a, Ravi Yadav6a, Sandhya K7b, Utpal Tatu8c, Pramod Kumar Pal6a#, Phalguni Anand Alladi1a* 1. Department of Clinical Psychopharmacology & Neurotoxicology 2. Department of Clinical Neurosciences 3. Department of Clinical Psychology 4. Department of Biostatistics 5. Department of Neuroimaging & Interventional Radiology 6. Department of Neurology 7. Department of Anaesthesiology 8. Department of Biochemistry a. National Institute of Mental Health and Neuro Sciences, Bengaluru, India b. Bangalore Medical College and Research Institute, Bengaluru, India c. Indian Institute of Science, Bengaluru, India *Corresponding Author: # Joint Corresponding Author Dr. Phalguni Anand Alladi Dr. Pramod Kumar Pal Senior Scientific Officer- Scientist ‘F’ Professor, Department of Neurology, Department of Clinical Psychopharmacology NIMHANS Parkinson's Disease & Movement and Neurotoxicology Disorders Subspeciality, National Institute of Mental Health & Neuro National Institute of Mental Health & Neuro Sciences, Hosur Road Bengaluru, 560029, Sciences, Hosur Road Bengaluru, 560029, Karnataka, INDIA Karnataka, INDIA Email: [email protected] [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2021.03.19.436097; this version posted March 19, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]