System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ppublish

PubMed: 40499536 DOI: 10.1016/j.neuron.2025.05.019

The cell-surface shared proteome of astrocytes and neurons and the molecular foundations of their multicellular interactions.

Neuron 113(16):2599-2620.e7

Authors: Ling Wu, Vijaya Pandey, Vanessa H Casha, Zhe Qu, Yasaman Jami-Alahmadi, Viviana Gradinaru, James A Wohlschlegel, Baljit S Khakh

Affiliations

  • Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
  • Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
  • Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.

Abstract

Neurons and astrocytes are predominant brain cells that extensively interact, but the molecular basis of their interactions remains largely unexplored. We identified and mapped striatal astrocytic and neuronal cell-surface proteins (CSPs) and found that many were shared, representing the cell-surface shared proteome of astrocytes and neurons (CS SPAN) bridging striatal astrocyte-neuron interaction sites. CS SPAN was replete with extracellular matrix proteins, cell adhesion molecules, transporters, ion channels, and G protein-coupled receptors. By mapping the cellular origins of astrocytic CSPs, we identified astrocytic interactions with diverse parenchymal cells. Broadly concordant with human data, in a mouse model of Huntington's disease (HD), pathophysiology and its genetic attenuation were accompanied by altered and restored CS SPAN and CSPs, respectively. CS SPAN also included molecules dysregulated in diverse brain disorders. Our study reveals the astrocyte-neuron interface in molecular terms and provides a mechanistic foundation for exploring its physiological roles and contributions to brain diseases.

MeSH

Cells, Astrocytes, Neurons, Horseradish Peroxidase, Brain, Neuroglia, Brain Diseases, Proteomics, Foundations, Proteome, Extracellular Matrix

Cited by