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MIRAVA POLYSCOPE – All in one and on for all: the perfect image
Science beyond Barriers

abberior instruments

All-purpose, Cell Biology, Neurobiology

2024
Molecular Psychiatry

The schizophrenia risk gene C4 induces pathological synaptic loss by impairing AMPAR trafficking

Authors:

Rhushikesh A. Phadke, Alison Brack, Luke A. Fournier, Ezra Kruzich, Mingqi Sha, Ines Picard, Connor Johnson, Dimitri Stroumbakis, Maria Salgado, Charlotte Yeung, Berta Escude Velasco, Yen Yu Liu, Alberto Cruz-Martín

Keywords:

Cell biology; Molecular biology; Neuroscience; Schizophrenia; AMPAR; complement receptor 3; CR3; SNX27; synaptic plasticity; endo-lysosomal trafficking

Abstract:

Neuroimmune interactions play a significant role in regulating synaptic plasticity in both the healthy and diseased brain. The complement pathway, an extracellular proteolytic cascade, exemplifies these interactions. Its activation triggers microglia-dependent synaptic elimination via the complement receptor 3 (CR3). Current models of pathological complement activity in the brain propose that accelerated synaptic loss resulting from overexpression of C4 (C4-OE), a gene associated with schizophrenia, follows this pathway. Here, we report that C4-mediated cortical hypoconnectivity is CR3-independent. Instead, C4-OE triggers impaired GluR1 trafficking through an intracellular mechanism involving the endosomal protein SNX27, resulting in pathological synaptic loss. Moreover, C4 circuit alterations in the prefrontal cortex, a brain region associated with neuropsychiatric disorders, were rescued by increasing neuronal levels of SNX27, which we identify as an interacting partner of this neuroimmune protein. Our results link excessive complement activity to an intracellular endo-lysosomal trafficking pathway altering synaptic plasticity.

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Superresolution & Confocal Systems

  • Overview
  • MINFLUX
  • MIRAVA POLYSCOPE
  • INFINITY
  • FACILITY
  • STEDYCON
  • Software Overview
  • LiGHTBOX
  • STEDYCON smart control
  • iMSPECTOR

Superresolution & Confocal Modules

  • Overview
  • MINFLUX Module
  • MATRIX Detector
  • TIMEBOW Imaging
  • FLEXPOSURE Illumination
  • RAYSHAPE Mirror
  • TRUESHARP Deconvolution
  • EASY3D
  • RAINBOW Detection
  • STED Lasers
  • Autoalignment
  • Autofocus
  • Excitation Lasers
  • Accessories
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Dyes & Labels

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  • abberior STAR
  • abberior LIVE
  • abberior FLUX
  • abberior CAGE
  • abberior Supplies

Shop

  • Dyes by Product Name
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  • Dyes by Label
  • Mounting Medium
  • Cells and Nanoparticles

Applications

  • Overview
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  • Live Cell Imaging
  • Material Science
  • Membrane biology
  • Microbiology
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  • Virology
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