ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Figure 1Loading Img

Interactome Analysis Reveals Regulator of G Protein Signaling 14 (RGS14) is a Novel Calcium/Calmodulin (Ca2+/CaM) and CaM Kinase II (CaMKII) Binding Partner

  • Paul R. Evans
    Paul R. Evans
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, United States
  • Kyle J. Gerber
    Kyle J. Gerber
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, United States
  • Eric B. Dammer
    Eric B. Dammer
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, United States
  • Duc M. Duong
    Duc M. Duong
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, United States
    More by Duc M. Duong
  • Devrishi Goswami
    Devrishi Goswami
    Department of Molecular Medicine, The Scripps Research Institute, Jupiter, Florida 33458, United States
  • Daniel J. Lustberg
    Daniel J. Lustberg
    Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, United States
  • Juan Zou
    Juan Zou
    Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30303, United States
    More by Juan Zou
  • Jenny J. Yang
    Jenny J. Yang
    Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30303, United States
  • Serena M. Dudek
    Serena M. Dudek
    Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, United States
  • Patrick R. Griffin
    Patrick R. Griffin
    Department of Molecular Medicine, The Scripps Research Institute, Jupiter, Florida 33458, United States
  • Nicholas T. Seyfried
    Nicholas T. Seyfried
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, United States
  • , and 
  • John R. Hepler*
    John R. Hepler
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, United States
    *E-mail: [email protected]. Phone: (404) 727-3641.
Cite this: J. Proteome Res. 2018, 17, 4, 1700–1711
Publication Date (Web):March 8, 2018
https://doi.org/10.1021/acs.jproteome.8b00027
Copyright © 2018 American Chemical Society

    Article Views

    835

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options
    Supporting Info (1)»

    Abstract

    Abstract Image

    Regulator of G Protein Signaling 14 (RGS14) is a complex scaffolding protein that integrates G protein and MAPK signaling pathways. In the adult mouse brain, RGS14 is predominantly expressed in hippocampal CA2 neurons where it naturally inhibits synaptic plasticity and hippocampus-dependent learning and memory. However, the signaling proteins that RGS14 natively engages to regulate plasticity are unknown. Here, we show that RGS14 exists in a high-molecular-weight protein complex in brain. To identify RGS14 neuronal interacting partners, endogenous RGS14 immunoprecipitated from mouse brain was subjected to mass spectrometry and proteomic analysis. We find that RGS14 interacts with key postsynaptic proteins that regulate plasticity. Gene ontology analysis reveals the most enriched RGS14 interactors have functional roles in actin-binding, calmodulin(CaM)-binding, and CaM-dependent protein kinase (CaMK) activity. We validate these findings using biochemical assays that identify interactions with two previously unknown binding partners. We report that RGS14 directly interacts with Ca2+/CaM and is phosphorylated by CaMKII in vitro. Lastly, we detect that RGS14 associates with CaMKII and CaM in hippocampal CA2 neurons. Taken together, these findings demonstrate that RGS14 is a novel CaM effector and CaMKII phosphorylation substrate thereby providing new insight into mechanisms by which RGS14 controls plasticity in CA2 neurons.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jproteome.8b00027.

    • Supplemental Table 1: table of complete spectra of MaxQuant protein groups’ output; Supplemental Table 2: table of enrichment statistics for proteins identified in IP samples (ZIP)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 16 publications.

    1. Kyle J. Gerber, Eric B. Dammer, Duc M. Duong, Qiudong Deng, Serena M. Dudek, Nicholas T. Seyfried, John R. Hepler. Specific Proteomes of Hippocampal Regions CA2 and CA1 Reveal Proteins Linked to the Unique Physiology of Area CA2. Journal of Proteome Research 2019, 18 (6) , 2571-2584. https://doi.org/10.1021/acs.jproteome.9b00103
    2. Tatyana Mamonova, Peter A. Friedman. The Molecular Sociology of NHERF1 PDZ Proteins Controlling Renal Hormone-Regulated Phosphate Transport. Bioscience Reports 2024, https://doi.org/10.1042/BSR20231380
    3. Mahsa Samadi, Claire A. Hales, Daniel J. Lustberg, Shannon Farris, Madeleine R. Ross, Meilan Zhao, John R. Hepler, Nicholas H. Harbin, Emma S. J. Robinson, Paul J. Banks, Zafar I. Bashir, Serena M. Dudek. Mechanisms of mGluR ‐dependent plasticity in hippocampal area CA2. Hippocampus 2023, 33 (6) , 730-744. https://doi.org/10.1002/hipo.23529
    4. N.H. Harbin, D.J. Lustberg, C. Hurst, J. Pare, K.M. Crotty, A.L. Waters, S.M. Yeligar, Y. Smith, N.T. Seyfried, D. Weinshenker, J.R. Hepler. RGS14 limits seizure-induced mitochondrial oxidative stress and pathology in hippocampus. Neurobiology of Disease 2023, 181 , 106128. https://doi.org/10.1016/j.nbd.2023.106128
    5. Carolina Montanez‐Miranda, Sara N. Bramlett, John R. Hepler. RGS14 expression in CA2 hippocampus, amygdala, and basal ganglia: Implications for human brain physiology and disease. Hippocampus 2023, 33 (3) , 166-181. https://doi.org/10.1002/hipo.23492
    6. João P.D. Machado, Maria C.P. Athie, Alexandre H.B. Matos, Iscia Lopes-Cendes, André.S. Vieira. The transcriptome of rat hippocampal subfields. IBRO Neuroscience Reports 2022, 13 , 322-329. https://doi.org/10.1016/j.ibneur.2022.09.009
    7. Peter A. Friedman, W. Bruce Sneddon, Tatyana Mamonova, Carolina Montanez-Miranda, Suneela Ramineni, Nicholas H. Harbin, Katherine E. Squires, Julia V. Gefter, Clara E. Magyar, David R. Emlet, John R. Hepler. RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein. Journal of Biological Chemistry 2022, 298 (5) , 101836. https://doi.org/10.1016/j.jbc.2022.101836
    8. Wenji Hu, Minkai Song, Chunyue Wang, Ziang Guo, Yu Li, Di Wang. Structural characterization of polysaccharide purified from Hericium erinaceus fermented mycelium and its pharmacological basis for application in Alzheimer's disease: Oxidative stress related calcium homeostasis. International Journal of Biological Macromolecules 2021, 193 , 358-369. https://doi.org/10.1016/j.ijbiomac.2021.10.117
    9. Stephanie L. Foster, Daniel J. Lustberg, Nicholas H. Harbin, Sara N. Bramlett, John R. Hepler, David Weinshenker. RGS14 modulates locomotor behavior and ERK signaling induced by environmental novelty and cocaine within discrete limbic structures. Psychopharmacology 2021, 238 (10) , 2755-2773. https://doi.org/10.1007/s00213-021-05892-x
    10. Nicholas H. Harbin, Sara N. Bramlett, Carolina Montanez-Miranda, Gizem Terzioglu, John R. Hepler. RGS14 Regulation of Post-Synaptic Signaling and Spine Plasticity in Brain. International Journal of Molecular Sciences 2021, 22 (13) , 6823. https://doi.org/10.3390/ijms22136823
    11. Katherine E. Squires, Kyle J. Gerber, Matthew C. Tillman, Daniel J. Lustberg, Carolina Montañez-Miranda, Meilan Zhao, Suneela Ramineni, Christopher D. Scharer, Ramendra N. Saha, Feng-Jue Shu, Jason P. Schroeder, Eric A. Ortlund, David Weinshenker, Serena M. Dudek, John R. Hepler. Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons. Journal of Biological Chemistry 2021, 296 , 100024. https://doi.org/10.1074/jbc.RA120.016009
    12. Faris Almutairi, Jae-Kyung Lee, Balázs Rada. Regulator of G protein signaling 10: Structure, expression and functions in cellular physiology and diseases. Cellular Signalling 2020, 75 , 109765. https://doi.org/10.1016/j.cellsig.2020.109765
    13. Arti Gautam, Poonam Pandey, Akhilesh Kumar Pandey. Proteomics in relation to abiotic stress tolerance in plants. 2020, 513-541. https://doi.org/10.1016/B978-0-12-818204-8.00023-0
    14. Joseph B. O’Brien, Joshua C. Wilkinson, David L. Roman. Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials. Journal of Biological Chemistry 2019, 294 (49) , 18571-18585. https://doi.org/10.1074/jbc.REV119.007060
    15. Kelly E Carstens, Serena M Dudek. Regulation of synaptic plasticity in hippocampal area CA2. Current Opinion in Neurobiology 2019, 54 , 194-199. https://doi.org/10.1016/j.conb.2018.07.008
    16. Paul R. Evans, Paula Parra-Bueno, Michael S. Smirnov, Daniel J. Lustberg, Serena M. Dudek, John R. Hepler, Ryohei Yasuda. RGS14 Restricts Plasticity in Hippocampal CA2 by Limiting Postsynaptic Calcium Signaling. eneuro 2018, 5 (3) , ENEURO.0353-17.2018. https://doi.org/10.1523/ENEURO.0353-17.2018

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect