Tissue-specific alternative splicing remodels protein-protein interaction networks

Mol Cell. 2012 Jun 29;46(6):884-92. doi: 10.1016/j.molcel.2012.05.037.


Alternative splicing plays a key role in the expansion of proteomic and regulatory complexity, yet the functions of the vast majority of differentially spliced exons are not known. In this study, we observe that brain and other tissue-regulated exons are significantly enriched in flexible regions of proteins that likely form conserved interaction surfaces. These proteins participate in significantly more interactions in protein-protein interaction (PPI) networks than other proteins. Using LUMIER, an automated PPI assay, we observe that approximately one-third of analyzed neural-regulated exons affect PPIs. Inclusion of these exons stimulated and repressed different partner interactions at comparable frequencies. This assay further revealed functions of individual exons, including a role for a neural-specific exon in promoting an interaction between Bridging Integrator 1 (Bin1)/Amphiphysin II and Dynamin 2 (Dnm2) that facilitates endocytosis. Collectively, our results provide evidence that regulated alternative exons frequently remodel interactions to establish tissue-dependent PPI networks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Alternative Splicing*
  • Binding Sites
  • Cells, Cultured
  • Dynamin II / genetics
  • Dynamin II / metabolism
  • Exons
  • HEK293 Cells
  • Humans
  • Luciferases, Renilla / genetics
  • Luciferases, Renilla / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Interaction Maps*
  • Proteins / genetics
  • Proteins / metabolism*
  • Proteomics
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism


  • Adaptor Proteins, Signal Transducing
  • BIN1 protein, human
  • Nuclear Proteins
  • Proteins
  • Tumor Suppressor Proteins
  • Luciferases, Renilla
  • Dynamin II