title: Tissue-specific alternative splicing remodels protein-protein interaction networks.
abstract: 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.
authors: Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
authors: Jonathan D
authors: JD
authors: Ellis
authors: Miriam
authors: M
authors: Barrios-Rodiles
authors: Recep
authors: R
authors: Colak
authors: Manuel
authors: M
authors: Irimia
authors: Taehyung
authors: T
authors: Kim
authors: John A
authors: JA
authors: Calarco
authors: Xinchen
authors: X
authors: Wang
authors: Qun
authors: Q
authors: Pan
authors: Dave
authors: D
authors: O'Hanlon
authors: Philip M
authors: PM
authors: Kim
authors: Jeffrey L
authors: JL
authors: Wrana
authors: Benjamin J
authors: BJ
authors: Blencowe
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D017398:Alternative Splicing; D001665:Binding Sites; D002478:Cells, Cultured; D034285:Dynamin II / Q000235:genetics / Q000378:metabolism; D005091:Exons; D057809:HEK293 Cells; D006801:Humans; D049410:Luciferases, Renilla / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D060066:Protein Interaction Maps; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D009687:Nuclear Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D049410:Luciferases, Renilla; D034285:Dynamin II