Macromolecular connectivity landscape of mammalian brain

Pourhaghighi et al.

  • Connectivity webs mediate the unique biology of the mammalian brain. Yet while cell circuit maps are increasingly available, knowledge of the underlying molecular networks remains limited. Here we applied multi-dimensional biochemical fractionation with precision mass spectrometry and machine learning to survey endogenous macromolecules in adult mouse brain. We defined a global ‘interactome’ of multi-protein complexes, most never reported before. These brain-selective assemblies have distinct physical and functional attributes and show regional and cell-type specificity. A striking number are also linked to neurological disorders and disease variants with broad pathophysiological relevance. Using reciprocal pulldowns and a transgenic model, we validated a putative 28-member RNA-binding protein complex associated with amyotrophic lateral sclerosis, establishing regulatory functions in alternative splicing and disease progression. This Brain Interaction Map – or ‘BraInMap’ – resource facilitates mechanistic exploration of the molecular machinery driving core processes and diseases of the central nervous system

  • From this website, you can access and download interactions and complexes for the BraInMap Proteins analyzed in this study.

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