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. 2025 Aug 20;113(16):2599-2620.e7.
doi: 10.1016/j.neuron.2025.05.019. Epub 2025 Jun 10.

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

Ling Wu  1 , Vijaya Pandey  2 , Vanessa H Casha  1 , Zhe Qu  3 , Yasaman Jami-Alahmadi  2 , Viviana Gradinaru  3 , James A Wohlschlegel  2 , Baljit S Khakh  4
Affiliations

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

Ling Wu et al. Neuron. .

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.

Keywords: Huntington's disease; astrocyte; cell-surface proteins; extracellular matrix; glia; horseradish peroxidase; neuron; proteomics; striatum.

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Conflict of interest statement

Declaration of interests B.S.K. is on the editorial advisory board of Neuron.

References

    1. Allen NJ, and Lyons DA (2018). Glia as architects of central nervous system formation and function. Science (New York, N.Y.) 362, 181–185. DOI: 10.1126/science.aat0473 - DOI - PMC - PubMed
    1. Yao Z, van Velthoven CTJ, Kunst M, Zhang M, McMillen D, Lee C, Jung W, Goldy J, Abdelhak A, Aitken M, et al. (2023). A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain. Nature 624, 317–332. 10.1038/s41586-023-06812-z. - DOI - PMC - PubMed
    1. Zhang M, Pan X, Jung W, Halpern AR, Eichhorn SW, Lei Z, Cohen L, Smith KA, Tasic B, Yao Z, et al. (2023). Molecularly defined and spatially resolved cell atlas of the whole mouse brain. Nature 624, 343–354. 10.1038/s41586-023-06808-9. - DOI - PMC - PubMed
    1. Langlieb J, Sachdev NS, Balderrama KS, Nadaf NM, Raj M, Murray E, Webber JT, Vanderburg C, Gazestani V, Tward D, et al. (2023). The molecular cytoarchitecture of the adult mouse brain. Nature 624, 333–342. 10.1038/s41586-023-06818-7. - DOI - PMC - PubMed
    1. Siletti K, Hodge R, Mossi Albiach A, Lee KW, Ding SL, Hu L, Lönnerberg P, Bakken T, Casper T, Clark M, et al. (2023). Transcriptomic diversity of cell types across the adult human brain. Science (New York, N.Y.) 382, eadd7046. 10.1126/science.add7046. - DOI - PubMed

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