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Contrastsing synaptic roles of MDGA1 and MDGA2.
Bemben, Michael A; Sandoval, Matthew; Le, Aliza A; Won, Sehoon; Chau, Vivian N; Lauterborn, Julie C; Incontro, Salvatore; Li, Kathy H; Burlingame, Alma L; Roche, Katherine W; Gall, Christine M; Nicoll, Roger A; Diaz-Alonso, Javier.
Afiliação
  • Bemben MA; Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA.
  • Sandoval M; Department of Anatomy & Neurobiology, University of California at Irvine, CA, 92617, USA.
  • Le AA; Center for the Neurobiology of Learning and Memory, University of California at Irvine, CA, USA.
  • Won S; Department of Anatomy & Neurobiology, University of California at Irvine, CA, 92617, USA.
  • Chau VN; Center for the Neurobiology of Learning and Memory, University of California at Irvine, CA, USA.
  • Lauterborn JC; Receptor Biology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
  • Incontro S; Department of Anatomy & Neurobiology, University of California at Irvine, CA, 92617, USA.
  • Li KH; Center for the Neurobiology of Learning and Memory, University of California at Irvine, CA, USA.
  • Burlingame AL; Department of Anatomy & Neurobiology, University of California at Irvine, CA, 92617, USA.
  • Roche KW; Center for the Neurobiology of Learning and Memory, University of California at Irvine, CA, USA.
  • Gall CM; Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA 94158, USA.
  • Nicoll RA; Present address: Unité de Neurobiologie des canaux Ioniques et de la Synapse (UNIS), UMR1072, INSERM, Aix-Marseille University, Marseille, 13015, France.
  • Diaz-Alonso J; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
bioRxiv ; 2023 May 26.
Article em En | MEDLINE | ID: mdl-37720016
Neurodevelopmental disorders are frequently linked to mutations in synaptic organizing molecules. MAM domain containing glycosylphosphatidylinositol anchor 1 and 2 (MDGA1 and MDGA2) are a family of synaptic organizers suggested to play an unusual role as synaptic repressors, but studies offer conflicting evidence for their localization. Using epitope-tagged MDGA1 and MDGA2 knock-in mice, we found that native MDGAs are expressed throughout the brain, peaking early in postnatal development. Surprisingly, endogenous MDGA1 was enriched at excitatory, but not inhibitory, synapses. Both shRNA knockdown and CRISPR/Cas9 knockout of MDGA1 resulted in cell-autonomous, specific impairment of AMPA receptor-mediated synaptic transmission, without affecting GABAergic transmission. Conversely, MDGA2 knockdown/knockout selectively depressed NMDA receptor-mediated transmission but enhanced inhibitory transmission. Our results establish that MDGA2 acts as a synaptic repressor, but only at inhibitory synapses, whereas both MDGAs are required for excitatory transmission. This nonoverlapping division of labor between two highly conserved synaptic proteins is unprecedented.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos