IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31264-w.html
   My bibliography  Save this article

Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity

Author

Listed:
  • Raphaël Dos Reis

    (INM, Université Montpellier, CNRS, INSERM)

  • Etienne Kornobis

    (C2RT, Institut Pasteur
    Hub Bioinformatique et Biostatistique, Département de Biologie Computationnelle – USR 3756 CNRS, Institut Pasteur)

  • Alyssa Pereira

    (INM, Université Montpellier, CNRS, INSERM)

  • Frederic Tores

    (BIP-D Plateforme de Bioinformatique Paris-Descartes, Institut Imagine)

  • Judit Carrasco

    (UMR 3738, Unité de Régulation Épigénétique, Institut Pasteur
    Max Planck Institute of Immunobiology and epigenetics)

  • Candice Gautier

    (Institut Imagine, INSERM - U1163, Unité mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques)

  • Céline Jahannault-Talignani

    (INM, Université Montpellier, CNRS, INSERM)

  • Patrick Nitschké

    (BIP-D Plateforme de Bioinformatique Paris-Descartes, Institut Imagine)

  • Christian Muchardt

    (UMR 3738, Unité de Régulation Épigénétique, Institut Pasteur)

  • Andreas Schlosser

    (University of Würzburg)

  • Hans Michael Maric

    (University of Würzburg, Biotechnology and Biophysics, Rudolf Virchow Zentrum Gebäude D15)

  • Fabrice Ango

    (INM, Université Montpellier, CNRS, INSERM)

  • Eric Allemand

    (UMR 3738, Unité de Régulation Épigénétique, Institut Pasteur
    Institut Imagine, INSERM - U1163, Unité mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques)

Abstract

Gephyrin (GPHN) regulates the clustering of postsynaptic components at inhibitory synapses and is involved in pathophysiology of neuropsychiatric disorders. Here, we uncover an extensive diversity of GPHN transcripts that are tightly controlled by splicing during mouse and human brain development. Proteomic analysis reveals at least a hundred isoforms of GPHN incorporated at inhibitory Glycine and gamma-aminobutyric acid A receptors containing synapses. They exhibit different localization and postsynaptic clustering properties, and altering the expression level of one isoform is sufficient to affect the number, size, and density of inhibitory synapses in cerebellar Purkinje cells. Furthermore, we discovered that splicing defects reported in neuropsychiatric disorders are carried by multiple alternative GPHN transcripts, demonstrating the need for a thorough analysis of the GPHN transcriptome in patients. Overall, we show that alternative splicing of GPHN is an important genetic variation to consider in neurological diseases and a determinant of the diversity of postsynaptic inhibitory synapses.

Suggested Citation

  • Raphaël Dos Reis & Etienne Kornobis & Alyssa Pereira & Frederic Tores & Judit Carrasco & Candice Gautier & Céline Jahannault-Talignani & Patrick Nitschké & Christian Muchardt & Andreas Schlosser & Han, 2022. "Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31264-w
    DOI: 10.1038/s41467-022-31264-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31264-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31264-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Donny D. Licatalosi & Aldo Mele & John J. Fak & Jernej Ule & Melis Kayikci & Sung Wook Chi & Tyson A. Clark & Anthony C. Schweitzer & John E. Blume & Xuning Wang & Jennifer C. Darnell & Robert B. Darn, 2008. "HITS-CLIP yields genome-wide insights into brain alternative RNA processing," Nature, Nature, vol. 456(7221), pages 464-469, November.
    2. Hans Michael Maric & Vikram Babu Kasaragod & Torben Johann Hausrat & Matthias Kneussel & Verena Tretter & Kristian Strømgaard & Hermann Schindelin, 2014. "Molecular basis of the alternative recruitment of GABAA versus glycine receptors through gephyrin," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    3. Thomas A. Ray & Kelly Cochran & Chris Kozlowski & Jingjing Wang & Graham Alexander & Martha A. Cady & William J. Spencer & Philip A. Ruzycki & Brian S. Clark & Annelies Laeremans & Ming-Xiao He & Xiao, 2020. "Comprehensive identification of mRNA isoforms reveals the diversity of neural cell-surface molecules with roles in retinal development and disease," Nature Communications, Nature, vol. 11(1), pages 1-20, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Matvei Khoroshkin & Andrey Buyan & Martin Dodel & Albertas Navickas & Johnny Yu & Fathima Trejo & Anthony Doty & Rithvik Baratam & Shaopu Zhou & Sean B. Lee & Tanvi Joshi & Kristle Garcia & Benedict C, 2024. "Systematic identification of post-transcriptional regulatory modules," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Elizabeth A. Werren & Geneva R. LaForce & Anshika Srivastava & Delia R. Perillo & Shaokun Li & Katherine Johnson & Safa Baris & Brandon Berger & Samantha L. Regan & Christian D. Pfennig & Sonja Munnik, 2024. "TREX tetramer disruption alters RNA processing necessary for corticogenesis in THOC6 Intellectual Disability Syndrome," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    3. Tao Wang & Beibei Chen & MinSoo Kim & Yang Xie & Guanghua Xiao, 2014. "A Model-Based Approach to Identify Binding Sites in CLIP-Seq Data," PLOS ONE, Public Library of Science, vol. 9(4), pages 1-11, April.
    4. Areum Han & Peter Stoilov & Anthony J Linares & Yu Zhou & Xiang-Dong Fu & Douglas L Black, 2014. "De Novo Prediction of PTBP1 Binding and Splicing Targets Reveals Unexpected Features of Its RNA Recognition and Function," PLOS Computational Biology, Public Library of Science, vol. 10(1), pages 1-18, January.
    5. Shivali Patel & Alec N. Sexton & Madison S. Strine & Craig B. Wilen & Matthew D. Simon & Anna Marie Pyle, 2023. "Systematic detection of tertiary structural modules in large RNAs and RNP interfaces by Tb-seq," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. Wei Hu & Yangjun Wu & Qili Shi & Jingni Wu & Deping Kong & Xiaohua Wu & Xianghuo He & Teng Liu & Shengli Li, 2022. "Systematic characterization of cancer transcriptome at transcript resolution," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Xiangbin Ruan & Kaining Hu & Xiaochang Zhang, 2023. "PIE-seq: identifying RNA-binding protein targets by dual RNA-deaminase editing and sequencing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Haoran Zhu & Yuning Yang & Yunhe Wang & Fuzhou Wang & Yujian Huang & Yi Chang & Ka-chun Wong & Xiangtao Li, 2023. "Dynamic characterization and interpretation for protein-RNA interactions across diverse cellular conditions using HDRNet," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    9. Huijuan Feng & Xiang-Jun Lu & Suvrajit Maji & Linxi Liu & Dmytro Ustianenko & Noam D. Rudnick & Chaolin Zhang, 2024. "Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    10. Liang-Cui Chu & Pedro Arede & Wei Li & Erika C. Urdaneta & Ivayla Ivanova & Stuart W. McKellar & Jimi C. Wills & Theresa Fröhlich & Alexander Kriegsheim & Benedikt M. Beckmann & Sander Granneman, 2022. "The RNA-bound proteome of MRSA reveals post-transcriptional roles for helix-turn-helix DNA-binding and Rossmann-fold proteins," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    11. Arpiar Saunders & Kee Wui Huang & Cassandra Vondrak & Christina Hughes & Karina Smolyar & Harsha Sen & Adrienne C. Philson & James Nemesh & Alec Wysoker & Seva Kashin & Bernardo L. Sabatini & Steven A, 2022. "Ascertaining cells’ synaptic connections and RNA expression simultaneously with barcoded rabies virus libraries," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    12. André Corvelo & Martina Hallegger & Christopher W J Smith & Eduardo Eyras, 2010. "Genome-Wide Association between Branch Point Properties and Alternative Splicing," PLOS Computational Biology, Public Library of Science, vol. 6(11), pages 1-13, November.
    13. Zhiping Zhang & Bongmin Bae & Winston H. Cuddleston & Pedro Miura, 2023. "Coordination of alternative splicing and alternative polyadenylation revealed by targeted long read sequencing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31264-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.