DOCSLIB.ORG

Calcium Sensor Regulation of the Cav2.1 Ca Channel Contributes to Short-Term Synaptic Plasticity in Hippocampal Neurons

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Calcium Sensor Regulation of the Cav2.1 Ca Channel Contributes to Short-Term Synaptic Plasticity in Hippocampal Neurons 2+ Calcium sensor regulation of the CaV2.1 Ca channel contributes to short-term synaptic plasticity in hippocampal neurons Evanthia Nanoua, Jane M. Sullivanb, Todd Scheuera, and William A. Catteralla,1 aDepartment of Pharmacology, University of Washington, Seattle, WA 98195-7280; and bDepartment of Physiology & Biophysics, University of Washington, Seattle, WA 98195-7290 Contributed by William A. Catterall, December 15, 2015 (sent for review November 10, 2015; reviewed by Diane Lipscombe and Gerald W. Zamponi) + Short-term synaptic plasticity is induced by calcium (Ca2 ) accumu- their CaS regulatory site have reduced facilitation and slowed + lating in presynaptic nerve terminals during repetitive action po- depression of postsynaptic responses because of reduced Ca2 - 2+ 2+ 2+ tentials. Regulation of voltage-gated CaV2.1 Ca channels by Ca dependent facilitation and Ca -dependent inactivation of 2+ 2+ sensor proteins induces facilitation of Ca currents and synaptic CaV2.1 currents (21). The CaS proteins Ca -binding protein 1 2+ facilitation in cultured neurons expressing exogenous CaV2.1 chan- (CaBP-1), visinin-like protein-2 (VILIP-2), and neuronal Ca + nels. However, it is unknown whether this mechanism contributes sensor-1 (NCS-1) induce different degrees of Ca2 -dependent to facilitation in native synapses. We introduced the IM-AA muta- – + facilitation and inactivation of channel activity (22 26). Expres- tion into the IQ-like motif (IM) of the Ca2 sensor binding site. This sion of these different CaS proteins with CaV2.1 channels in mutation does not alter voltage dependence or kinetics of CaV2.1 cultured sympathetic ganglion neurons results in corresponding currents, or frequency or amplitude of spontaneous miniature ex- bidirectional changes in facilitation and depression of the post- citatory postsynaptic currents (mEPSCs); however, synaptic facili- synaptic response (25, 26). Therefore, binding of CaS proteins to tation is completely blocked in excitatory glutamatergic synapses CaV2.1 channels at specific synapses can change the balance of in hippocampal autaptic cultures. In acutely prepared hippocampal CaS-dependent facilitation and inactivation of CaV2.1 channels, slices, frequency and amplitude of mEPSCs and amplitudes of and determine the outcome of synaptic plasticity (27). Currently, NEUROSCIENCE evoked EPSCs are unaltered. In contrast, short-term synaptic facil- it is not known whether such molecular regulation of Ca 2.1 itation in response to paired stimuli is reduced by ∼50%. In the V + by CaS proteins induces or modulates synaptic plasticity in native presence of EGTA-AM to prevent global increases in free Ca2 , the hippocampal synapses. IM-AA mutation completely blocks short-term synaptic facilitation, + To understand the functional role of regulation of Ca 2.1 indicating that synaptic facilitation by brief, local increases in Ca2 V 2+ channels by CaS proteins in synaptic plasticity in vivo, we gen- is dependent upon regulation of CaV2.1 channels by Ca sensor erated knock-in mice with paired alanine substitutions for the proteins. In response to trains of action potentials, synaptic facil- isoleucine and methionine residues in the IM motif (IM-AA) in itation is reduced in IM-AA synapses in initial stimuli, consistent their C-terminal domain. Here we investigated the effects of with results of paired-pulse experiments; however, synaptic de- mutating this CaS regulatory site on hippocampal neurotrans- pression is also delayed, resulting in sustained increases in amplitudes mission and synaptic plasticity. This mutation had no effect on – + of later EPSCs during trains of 10 stimuli at 10 20 Hz. Evidently, reg- basal Ca2 channel function or on basal synaptic transmission. ulation of CaV2.1 channels by CaS proteins is required for normal However, we found reduced short-term facilitation in response short-term plasticity and normal encoding of information in native to paired stimuli in autaptic synapses in hippocampal cultures hippocampal synapses. and in Schaffer collateral (SC)-CA1 synapses in acutely prepared hippocampal slices. Moreover, synaptic facilitation in mutant SC-CA1 calcium channel | calcium sensor proteins | synaptic facilitation | calmodulin | hippocampus Significance odification of synaptic strength in central synapses is highly Information processing in the brain is mediated through syn- Mdependent upon presynaptic activity. The frequency and aptic connections between neurons, where neurotransmitter pattern of presynaptic action potentials regulates the post- molecules released from presynaptic nerve terminals stimulate synaptic response through diverse forms of short- and long-term postsynaptic cells. Strength of synaptic transmission is in- plasticity that are specific to individual synapses and depend creased transiently by short-term synaptic facilitationinresponse 2+ – upon accumulation of intracellular Ca (1 4). Presynaptic to repeated stimulation of nerve fibers. Synaptic transmission is plasticity regulates neurotransmission by varying the amount of initiated by calcium influx through calcium channels in presynaptic neurotransmitter released by each presynaptic action potential 2+ nerve terminals, which are regulated by calcium sensor proteins. (1–5). P/Q-type Ca currents conducted by voltage-gated CaV2.1 2+ We found that genetically modified mice in which we introduced Ca channels initiate neurotransmitter release at fast excitatory amutationinthebindingsiteforcalciumsensorproteinsinpre- glutamatergic synapses in the brain (6–9) and regulate short-term + synaptic calcium channels have substantially altered facilitation presynaptic plasticity (3, 10). These channels exhibit Ca2 -dependent 2+ in hippocampal synapses in response to pairs or trains of re- facilitation and inactivation that is mediated by the Ca sensor petitive high-frequency stimuli. Our results show that disrup- (CaS) protein calmodulin (CaM) bound to a bipartite site in their tion of calcium channel regulation by calcium sensor proteins C-terminal domain composed of an IQ-like motif (IM) and a CaM + impairs short-term facilitation in native synapses. binding domain (CBD) (11–14). Ca2 -dependent facilitation and 2+ inactivation of P/Q-type Ca currents correlate with facilitation and Author contributions: E.N., J.M.S., T.S., and W.A.C. designed research; E.N. performed rapid depression of synaptic transmission at the Calyx of Held (15– research; J.M.S. contributed new reagents/analytic tools; E.N., J.M.S., T.S., and W.A.C. analyzed data; and E.N., J.M.S., T.S., and W.A.C. wrote the paper. 18). Elimination of CaV2.1 channels by gene deletion prevents fa- cilitation of synaptic transmission at the Calyx of Held (19, 20). Reviewers: D.L., Brown University; and G.W.Z., University of Calgary. Cultured sympathetic ganglion neurons with presynaptic ex- The authors declare no conflict of interest. 1 pression of exogenous CaV2.1 channels harboring mutations in To whom correspondence should be addressed. Email: [email protected]. www.pnas.org/cgi/doi/10.1073/pnas.1524636113 PNAS Early Edition | 1of6 Downloaded by guest on September 24, 2021 ABC(P = 0.32). If it had any effect, the trend toward smaller EPSCs observed in these experiments would be expected to increase facilitation, thereby opposing the observed reduction of facili- tation by the IM-AA mutation. Hence, the IM-AA mutation in CaV2.1 channels does not alter basal synaptic transmission, but instead specifically blocks paired-pulse facilitation in hippocampal autaptic synapses. The IM-AA Mutation Reduces Short-Term Facilitation in Schaffer Collateral-CA1 Synapses. To extend our experiments to a more physiological synapse, we examined synaptic transmission and plasticity in acutely dissected hippocampal slices. We recorded Fig. 1. IM-AA mutation in CaV2.1 channels does not alter the kinetics of P/Q + Ca2 currents in cultured hippocampal neurons. (A) Mean-normalized from SC-CA1 synapses that have complex, but well-studied, CaV2.1-mediated ICa from WT (black, n = 23) and IM-AA (red, n = 27) evoked forms of synaptic plasticity. Spontaneously occurring mEPSCs by 1-s depolarizing test pulse from −80 to +10 mV. The traces shown are recorded in the presence of tetrodotoxin were unchanged in averages ± SEM. Enlarged time scale of the peak CaV2.1-mediated ICa is frequency and amplitude (Fig. 3). Because spontaneous mEPSCs shown in a dashed-line box. (B) Average peak CaV2.1-mediated ICa current result from activation of postsynaptic AMPA receptors (AMPAR) density from WT (black, n = 23) and IM-AA (red, n = 27). (C) Voltage de- by spontaneous presynaptic release of glutamate, these data show pendence of activation of I from WT (black, n = 23) and IM-AA (red, n = 27) Ca that CaV2.1/IM-AA mutation does not affect the spontaneous tail currents measured from a holding potential of −80 mV to the indicated release probability, the quantal size of the presynaptic release of potential. n indicates the number of cells recorded in each genotype. glutamate, or the AMPAR-dependent peak of the postsynaptic response at this synapse. We measured excitatory responses of CA1 pyramidal neurons synapses developed and decayed more slowly during trains of in response to extracellular stimuli applied to SC fibers. The stimuli. These results identify a critical role for modulation of input–output relationship of evoked EPSCs was not changed in Ca 2.1 channels by CaS proteins in short-term synaptic plastic- V hippocampal slices from IM-AA mice (Fig. 4 A and B), indi- ity, which is likely to have important
Load more

Recommended publications
  • Altered Calcium Handling in Cerebellar Purkinje Neurons with the Malignant Hyperthermia Mutation, Ryr1-Y522S/+
    University of Denver Digital Commons @ DU Electronic Theses and Dissertations Graduate Studies 1-1-2011 Altered Calcium Handling in Cerebellar Purkinje Neurons with the Malignant Hyperthermia Mutation, RyR1-Y522S/+ George C. Talbott University of Denver Follow this and additional works at: https://digitalcommons.du.edu/etd Part of the Biochemistry, Biophysics, and Structural Biology Commons, and the Biology Commons Recommended Citation Talbott, George C., "Altered Calcium Handling in Cerebellar Purkinje Neurons with the Malignant Hyperthermia Mutation, RyR1-Y522S/+" (2011). Electronic Theses and Dissertations. 638. https://digitalcommons.du.edu/etd/638 This Thesis is brought to you for free and open access by the Graduate Studies at Digital Commons @ DU. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of Digital Commons @ DU. For more information, please contact [email protected],[email protected]. ALTERED CALCIUM HANDLING IN CEREBELLAR PURKINJE NEURONS WITH THE MALIGNANT HYPERTHERMIA MUTATION, RYR1 Y522S/+ __________ A Thesis Presented to The Faculty of Natural Sciences and Mathematics University of Denver __________ In Partial Fulfillment of the Requirements for the Degree Master of Science __________ by George C. Talbott June 2011 Advisor: Nancy M. Lorenzon, PhD ©Copyright by George C. Talbott 2011 All Rights Reserved Author: George C. Talbott Title: ALTERED CALCIUM HANDLING IN CEREBELLAR PURKINJE NEURONS WITH THE MALIGNANT HYPERTHERMIA MUTATION, RYR1 Y522S/+ Advisor: Nancy M. Lorenzon, PhD Degree Date: June 2011 Abstract To investigate the etiology of malignant hyperthermia and central core disease, mouse models have recently been generated and characterized (Chelu et al., 2006). These RyR Y522S/+ knock-in mutant mice provide an excellent tool to investigate calcium dysregulation, its pathological consequences, and potential therapeutic approaches.
    [Show full text]
  • Myoplasmic Resting Ca2+ Regulation by Ryanodine Receptors Is
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Georgia State University Georgia State University ScholarWorks @ Georgia State University Chemistry Faculty Publications Department of Chemistry 2014 Myoplasmic resting Ca2+ regulation by ryanodine receptors is under the control of a novel Ca2+- binding region of the receptor Yanyi Chen Georgia State University, [email protected] Shenghui Xue Georgia State University, [email protected] Juan Zou Georgia State University, [email protected] Jose Lopez University of California, Davis Jenny J. Yang Georgia State University, [email protected] See next page for additional authors Follow this and additional works at: http://scholarworks.gsu.edu/chemistry_facpub Part of the Chemistry Commons Recommended Citation Chen, Yanyi; Xue, Shenghui; Zou, Juan; Lopez, Jose; Yang, Jenny J.; and Perez, Claudio, "Myoplasmic resting Ca2+ regulation by ryanodine receptors is under the control of a novel Ca2+-binding region of the receptor" (2014). Chemistry Faculty Publications. Paper 10. http://scholarworks.gsu.edu/chemistry_facpub/10 This Article is brought to you for free and open access by the Department of Chemistry at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Chemistry Faculty Publications by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. Authors Yanyi Chen, Shenghui Xue, Juan Zou, Jose Lopez, Jenny J. Yang, and Claudio Perez This article is available at ScholarWorks @ Georgia State University: http://scholarworks.gsu.edu/chemistry_facpub/10 Biochem. J. (2014) 460, 261–271 (Printed in Great Britain) doi:10.1042/BJ20131553 261 Myoplasmic resting Ca2 + regulation by ryanodine receptors is under the control of a novel Ca2 + -binding region of the receptor Yanyi CHEN*1, Shenghui XUE*1, Juan ZOU*, Jose R.
    [Show full text]
  • Neuronal Calcium Sensor-1 Modulation of Optimal Calcium Level for Neurite Outgrowth Kwokyin Hui1, Guang-He Fei1, Bechara J
    RESEARCH ARTICLE 4479 Development 134, 4479-4489 (2007) doi:10.1242/dev.008979 Neuronal calcium sensor-1 modulation of optimal calcium level for neurite outgrowth Kwokyin Hui1, Guang-He Fei1, Bechara J. Saab2,3, Jiang Su1, John C. Roder2,3 and Zhong-Ping Feng1,* Neurite extension and branching are affected by activity-dependent modulation of intracellular Ca2+, such that an optimal window 2+ 2+ of [Ca ]i is required for outgrowth. Our understanding of the molecular mechanisms regulating this optimal [Ca ]i remains unclear. Taking advantage of the large growth cone size of cultured primary neurons from pond snail Lymnaea stagnalis combined with dsRNA knockdown, we show that neuronal calcium sensor-1 (NCS-1) regulates neurite extension and branching, and activity- dependent Ca2+ signals in growth cones. An NCS-1 C-terminal peptide enhances only neurite branching and moderately reduces the Ca2+ signal in growth cones compared with dsRNA knockdown. Our findings suggest that at least two separate structural domains in NCS-1 independently regulate Ca2+ influx and neurite outgrowth, with the C-terminus specifically affecting branching. We describe a model in which NCS-1 regulates cytosolic Ca2+ around the optimal window level to differentially control neurite extension and branching. KEY WORDS: NCS-1, Neurite outgrowth, Activity-dependent calcium signals, fura-2 imaging, Lymnaea stagnalis INTRODUCTION There is compelling evidence that NCS-1 is involved in neurite Neurite extension and branching are affected by activity-dependent development in a few systems. For instance, NCS-1 expression modulation of intracellular Ca2+ (Komuro and Rakic, 1996; Tang et increases in grey matter and decreases in white matter during 2+ al., 2003; Zheng, 2000), such that an optimal window of [Ca ]i is embryogenesis and early postnatal stages (Kawasaki et al., 2003).
    [Show full text]
  • Modulation of Neuronal Ryanodine Receptor-Mediated Calcium
    MODULATION OF NEURONAL RYANODINE RECEPTOR-MEDIATED CALCIUM SIGNALING BY CALSENILIN A DISSERTATION IN Cell Biology and Biophysics and Molecular Biology and Biochemistry Presented to the Faculty of the University of Missouri-Kansas City in partial fulfillment of the requirements for the degree DOCTOR OF PHILOSOPHY by MICHAEL ANTHONY GRILLO M.S., University of Missouri-Kansas City, Kansas City, MO 2010 B.S., Texas Wesleyan University, TX, 2000 Kansas City, MO 2013 2013 MICHAEL ANTHONY GRILLO ALL RIGHTS RESERVED MODULATION OF NEURONAL RYANODINE RECEPTOR-MEDIATED CALCIUM SIGNALING BY CALSENILIN Michael Anthony Grillo, Candidate for the Doctor of Philosophy Degree University of Missouri-Kansas City, 2013 ABSTRACT Calsenilin is calcium (Ca2+) ion Ca2+ binding protein found in the nucleus, plasma membrane, and endoplasmic reticulum of neuronal cells. Calsenilin was first found to interact with two proteins involved in early-onset familial Alzheimer disease (AD), presenilin 1 and presenilin 2. Several studies have shown overexpression of calsenilin to alter Ca2+ signaling and cell viability in several neuronal cell models of AD. In this study, we show that calsenilin directly interacts with the ryanodine receptor (RyR) modulating Ca2+ release from this intracellular Ca2+-activated Ca2+ release channel. Co-expression, co-localization, and protein-protein interaction of calsenilin and RyR in primary neurons and in central nervous system tissue were determined using immunoblotting, immunohistochemistry and co-immunoprecipitation. Mechanisms of intracellular Ca2+- signaling controlled by the interaction of calsenilin and RyR, including changes in the release of Ca2+ from intracellular stores, were measured with single channel electrophysiology and live-cell optical imaging techniques. Immunohistochemical studies showed a high degree of co-localization between calsenilin and the RyR in neurons of the central nervous system.
    [Show full text]
  • Calbindin-D28k and Its Role in Apoptosis: Inhibition of Caspase-3 Activity and Interaction with Pro-Caspase-3 Investigated by In-Situ FRET Microscopy
    Dissertation Aus dem Physiologischen Institut Lehrstuhl: Physiologie – Zelluläre Physiologie (Biomedizinisches Zentrum München) der Ludwig-Maximilians-Universität München Vorstand: Prof. Dr. Claudia Veigel Calbindin-D28k and its role in apoptosis: Inhibition of Caspase-3 activity and interaction with Pro-Caspase-3 investigated by in-situ FRET microscopy. Dissertation zum Erwerb des Doktorgrades der Medizin an der Medizinischen Fakultät der Ludwig-Maximilians-Universität zu München vorgelegt von Johannes Lohmeier aus Bong Town, Liberia 2018 Mit Genehmigung der Medizinischen Fakultät der Universität München Berichterstatter: Prof. Dr. Michael Meyer Prof. Dr. Alexander Faussner Mitberichterstatter: Prof. Dr. Nikolaus Plesnila Prof. Dr. Dr. Bernd Sutor Dekan: Prof. Dr. med. dent. Reinhard Hickel Tag der mündlichen Prüfung: 14.06.2018 Eidesstattliche Versicherung Lohmeier, Johannes Name, Vorname Ich erkläre hiermit an Eides statt, dass ich die vorliegende Dissertation mit dem Thema Calbindin-D28k and its role in apoptosis: Inhibition of Caspase-3 activity and interaction with Pro-Caspase-3 investigated by in-situ FRET microscopy. selbständig verfasst, mich außer der angegebenen keiner weiteren Hilfsmittel bedient und alle Erkenntnisse, die aus dem Schrifttum ganz oder annähernd übernommen sind, als solche kenntlich gemacht und nach ihrer Herkunft unter Bezeichnung der Fundstelle einzeln nachgewiesen habe. Ich erkläre des Weiteren, dass die hier vorgelegte Dissertation nicht in gleicher oder in ähnlicher Form bei einer anderen Stelle zur Erlangung
    [Show full text]
  • A FAMILY of NEURONAL Ca2+-BINDING PROTEINS WITH
    Neuroscience Vol. 112, No. 1, pp. 51^63, 2002 ß 2002 IBRO. Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain PII: S0306-4522(02)00063-5 0306-4522 / 02 $22.00+0.00 www.neuroscience-ibro.com NECABS: A FAMILY OF NEURONAL Ca2þ-BINDING PROTEINS WITH AN UNUSUAL DOMAIN STRUCTURE AND A RESTRICTED EXPRESSION PATTERN S. SUGITA,1 A. HO and T. C. SUº DHOFÃ Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235, USA AbstractöCa2þ-signalling plays a major role in regulating all aspects of neuronal function. Di¡erent types of neurons exhibit characteristic di¡erences in the responses to Ca2þ-signals. Correlating with di¡erences in Ca2þ-response are expression patterns of Ca2þ-binding proteins that often serve as markers for various types of neurons. For example, in the cerebral cortex the EF-hand Ca2þ-binding proteins parvalbumin and calbindin are primarily expressed in inhibitory interneurons where they in£uence Ca2þ-dependent responses. We have now identi¢ed a new family of proteins called NECABs (neuronal Ca2þ-binding proteins). NECABs contain an N-terminal EF-hand domain that binds Ca2þ, but di¡erent from many other neuronal EF-hand Ca2þ-binding proteins, only a single EF-hand domain is present. At the C-terminus, NECABs include a DUF176 motif, a bacterial domain of unknown function that was previously not observed in eukaryotes. In rat at least three closely related NECAB genes are expressed either primarily in brain (NECABs 1 and 2) or in brain and muscle (NECAB 3).
    [Show full text]
  • Molecular Dynamics of the Neuronal Ca -Binding Proteins
    Molecular dynamics of the neuronal Ca2+ -binding proteins Caldendrin and Calneurons Dissertation zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) genehmigt durch die Fakultät für Naturwissenschaften der Otto-von-Guericke-Universität Magdeburg von Diplom-Biologin Marina Gennadievna Mikhaylova geb. am 1 März 1981 in Ufa, Russland Gutachter: Prof. Dr. E.D. Gundelfinger am: 30.07.2009 vorgelegt von: Diplom-Biologin Marina Gennadievna Mikhaylova Acknowledgements This thesis is the account of almost four years of devoted work at the Leibniz Institute for Neurobiology Magdeburg in the group of Michael R. Kreutz (Project Group Neuroplasticity) which would not have been possible without the help of many friends and colleagues. First of all, I would like to thank Michael for being a great advisor. His ideas and tremendous support had a major influence on this thesis. I want to thank Anna Karpova for being my friend and colleague for many years. I enjoyed to do research together with her as well as the nice discussions we daily had. Many thanks also to Prof. Eckart D Gundelfinger for his encouraging discussions and help with corrections of the papers. My thanks to Thomas Munsch, Peter Landgraf, Karl-Heinz Smalla, Ulrich Thomas, Oliver Kobler, Yogendra Sharma and Thomas Behnisch for the great collaboration over the years. It was a pleasure to work with all these people and to benefit from their knowledge. My thanks to Paramesh Pasham Reddy, Anne-Christin Lehman, Johannes Hradsky and Philipp Bethge for their collaboration, support and friendship while doing their Ph.D studies, diploma theses or internships in our group.
    [Show full text]
  • The Calcium Sensor Synaptotagmin 7 Is Required for Synaptic Facilitation
    The calcium sensor synaptotagmin 7 is required for synaptic facilitation The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Jackman, Skyler L., Josef Turecek, Justine E. Belinsky, and Wade G. Regehr. 2015. “The calcium sensor synaptotagmin 7 is required for synaptic facilitation.” Nature 529 (7584): 88-91. doi:10.1038/ nature16507. http://dx.doi.org/10.1038/nature16507. Published Version doi:10.1038/nature16507 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:27822294 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA HHS Public Access Author manuscript Author Manuscript Author ManuscriptNature. Author ManuscriptAuthor manuscript; Author Manuscript available in PMC 2016 July 07. Published in final edited form as: Nature. 2016 January 7; 529(7584): 88–91. doi:10.1038/nature16507. The calcium sensor synaptotagmin 7 is required for synaptic facilitation Skyler L. Jackman1, Josef Turecek1, Justine E. Belinsky1, and Wade G. Regehr1 1Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA Abstract It has been known for over 70 years that synaptic strength is dynamically regulated in a use- dependent manner1. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement where each subsequent action potential evokes greater neurotransmitter release2. Facilitation can enhance neurotransmitter release manyfold and profoundly influence information transfer across synapses3, but the underlying mechanism remains a mystery.
    [Show full text]
  • Supplementary Material Contents
    Supplementary Material Contents Immune modulating proteins identified from exosomal samples.....................................................................2 Figure S1: Overlap between exosomal and soluble proteomes.................................................................................... 4 Bacterial strains:..............................................................................................................................................4 Figure S2: Variability between subjects of effects of exosomes on BL21-lux growth.................................................... 5 Figure S3: Early effects of exosomes on growth of BL21 E. coli .................................................................................... 5 Figure S4: Exosomal Lysis............................................................................................................................................ 6 Figure S5: Effect of pH on exosomal action.................................................................................................................. 7 Figure S6: Effect of exosomes on growth of UPEC (pH = 6.5) suspended in exosome-depleted urine supernatant ....... 8 Effective exosomal concentration....................................................................................................................8 Figure S7: Sample constitution for luminometry experiments..................................................................................... 8 Figure S8: Determining effective concentration .........................................................................................................
    [Show full text]
  • Myoplasmic Resting Ca2+ Regulation by Ryanodine Receptors Is Under the Control of a Novel Ca2+-Binding Region of the Receptor
    Georgia State University ScholarWorks @ Georgia State University Chemistry Faculty Publications Department of Chemistry 2014 Myoplasmic resting Ca2+ regulation by ryanodine receptors is under the control of a novel Ca2+-binding region of the receptor Yanyi Chen Georgia State University, [email protected] Shenghui Xue Georgia State University, [email protected] Juan Zou Georgia State University, [email protected] Jose Lopez University of California, Davis Jenny J. Yang Georgia State University, [email protected] See next page for additional authors Follow this and additional works at: https://scholarworks.gsu.edu/chemistry_facpub Part of the Chemistry Commons Recommended Citation Chen, Yanyi; Xue, Shenghui; Zou, Juan; Lopez, Jose; Yang, Jenny J.; and Perez, Claudio, "Myoplasmic resting Ca2+ regulation by ryanodine receptors is under the control of a novel Ca2+-binding region of the receptor" (2014). Chemistry Faculty Publications. 10. https://scholarworks.gsu.edu/chemistry_facpub/10 This Article is brought to you for free and open access by the Department of Chemistry at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Chemistry Faculty Publications by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. Authors Yanyi Chen, Shenghui Xue, Juan Zou, Jose Lopez, Jenny J. Yang, and Claudio Perez This article is available at ScholarWorks @ Georgia State University: https://scholarworks.gsu.edu/chemistry_facpub/ 10 Biochem. J. (2014) 460, 261–271 (Printed in Great Britain) doi:10.1042/BJ20131553 261 Myoplasmic resting Ca2 + regulation by ryanodine receptors is under the control of a novel Ca2 + -binding region of the receptor Yanyi CHEN*1, Shenghui XUE*1, Juan ZOU*, Jose R.
    [Show full text]
  • New Approach for Untangling the Role of Uncommon Calcium-Binding Proteins in the Central Nervous System
    brain sciences Review New Approach for Untangling the Role of Uncommon Calcium-Binding Proteins in the Central Nervous System Krisztina Kelemen * and Tibor Szilágyi Department of Physiology, Doctoral School, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mures, , Romania; [email protected] * Correspondence: [email protected]; Tel.: +40-746-248064 Abstract: Although Ca2+ ion plays an essential role in cellular physiology, calcium-binding proteins (CaBPs) were long used for mainly as immunohistochemical markers of specific cell types in different regions of the central nervous system. They are a heterogeneous and wide-ranging group of proteins. Their function was studied intensively in the last two decades and a tremendous amount of informa- tion was gathered about them. Girard et al. compiled a comprehensive list of the gene-expression profiles of the entire EF-hand gene superfamily in the murine brain. We selected from this database those CaBPs which are related to information processing and/or neuronal signalling, have a Ca2+- buffer activity, Ca2+-sensor activity, modulator of Ca2+-channel activity, or a yet unknown function. In this way we created a gene function-based selection of the CaBPs. We cross-referenced these findings with publicly available, high-quality RNA-sequencing and in situ hybridization databases (Human Protein Atlas (HPA), Brain RNA-seq database and Allen Brain Atlas integrated into the HPA) and created gene expression heat maps of the regional and cell type-specific expression levels of the selected CaBPs. This represents a useful tool to predict and investigate different expression patterns and functions of the less-known CaBPs of the central nervous system.
    [Show full text]
  • Calcium Homeostasis and Regulation of Calbindin-D9k by Glucocorticoids and Vitamin D As Bioactive Molecules
    Biomolecules & Therapeutics, 17(2), 125-132 (2009) ISSN: 1976-9148(print)/2005-4483(online) www.biomolther.org DOI: 10.4062/biomolther.2009.17.2.125 Review Calcium Homeostasis and Regulation of Calbindin-D9k by Glucocorticoids and Vitamin D as Bioactive Molecules 2 1, Kyung-Chul CHOI , and Eui-Bae JEUNG * 1Laboratory of Veterinary Biochemistry and Molecular Biology and 2Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea (Received January 21, 2009; Revised March 26, 2009; Accepted March 31, 2009) Abstract － Calbindin-D9k (CaBP-9k), a cytosolic calcium-binding protein, is expressed in a variety of tissues, i.e., the duodenum, uterus, placenta, kidney and pituitary gland. Duodenal CaBP-9k is involved in intestinal calcium absorption, and is regulated at transcriptional and post-transcriptional levels by 1,25- dihydroxyvitamin D3, the hormonal form of vitamin D, and glucocorticoids (GCs). Uterine CaBP-9k has been implicated in the regulation of myometrial action(s) through modulation of intracellular calcium, and steroid hormones appear to be the main regulators in its uterine and placental regulation. Because phenotypes of CaBP-9k-null mice appear to be normal, other calcium-transporter genes may compensate for its gene deletion and physiological function in knockout mice. Previous studies indicate that CaBP-9k may be controlled in a tissue-specific fashion. In this review, we summarize the current information on calcium homeostasis related to CaBP-9k gene regulation by GCs, vitamin D and its receptors, and its molecular regulatory mechanism. In addition, we present related data from our current research.
    [Show full text]