VerteBrain reveals novel neuronal and non-neuronal protein assemblies conserved across vertebrate brains

Published

May 28, 2025

Author(s)

Vy Dang, Brittney Voigt, David Yang, Gabriel Hoogerbrugge, Muyoung Lee, Rachael Cox, Ophelia Papoulas, Claire McWhite, Raksha Pradeep, Janelle Leggere, Benjamin Neely, Ryan Gray, Edward Marcotte

Abstract

Protein-protein interactions in the vertebrate brain underlie key processes such as neurotransmitter release, receptor activation, and signaling pathways that are essential for learning, memory, and cognition. Here, we systematically map protein-protein interactions in brains from five vertebrate species using co-fractionation and immunoprecipitation mass spectrometry. From 2,197 biochemical fractions generated from brains of rabbit, chicken, dolphin, pig, and mouse, we identified over 82,000 high-confidence interactions among 6,108 conserved proteins. This protein interaction map reveals regulatory and structural complexes, and extensive synaptonemal protein associations consistent with bridging neurons. The evolutionary conservation of these interactions likely underscores essential roles in neuronal and glial function. We have already identified new links to human disease within this rich dataset including a role for ARHGEF1 in short stature disorders, and synaptic vesicle trafficking complexes tied to epilepsy and implicating RELCH in congenital deafness. The publicly available VerteBrain map provides a comprehensive framework for studying brain protein function and advancing research into neurological disorders.

Citation

Nature Methods

Pub Type

Journals

Keywords

High-throughput, comparative proteomics, neuroproteomics, cross-linking mass spectroscopy, protein-protein interactions

Citation

Dang, V. , Voigt, B. , Yang, D. , Hoogerbrugge, G. , Lee, M. , Cox, R. , Papoulas, O. , McWhite, C. , Pradeep, R. , Leggere, J. , Neely, B. , Gray, R. and Marcotte, E. (2025), VerteBrain reveals novel neuronal and non-neuronal protein assemblies conserved across vertebrate brains, Nature Methods (Accessed July 4, 2025)