title: Intersectin (ITSN) family of scaffolds function as molecular hubs in protein interaction networks.
abstract: Members of the intersectin (ITSN) family of scaffold proteins consist of multiple modular domains, each with distinct ligand preferences. Although ITSNs were initially implicated in the regulation of endocytosis, subsequent studies have revealed a more complex role for these scaffold proteins in regulation of additional biochemical pathways. In this study, we performed a high throughput yeast two-hybrid screen to identify additional pathways regulated by these scaffolds. Although several known ITSN binding partners were identified, we isolated more than 100 new targets for the two mammalian ITSN proteins, ITSN1 and ITSN2. We present the characterization of several of these new targets which implicate ITSNs in the regulation of the Rab and Arf GTPase pathways as well as regulation of the disrupted in schizophrenia 1 (DISC1) interactome. In addition, we demonstrate that ITSN proteins form homomeric and heteromeric complexes with each other revealing an added level of complexity in the function of these evolutionarily conserved scaffolds.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, USA.
authors.forename: Katy A
authors.initials: KA
authors.lastname: Wong
authors.forename: Jessica
authors.initials: J
authors.lastname: Wilson
authors.forename: Angela
authors.initials: A
authors.lastname: Russo
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Mustafa Nazir
authors.initials: MN
authors.lastname: Okur
authors.forename: Xuerong
authors.initials: X
authors.lastname: Wang
authors.forename: Negin P
authors.initials: NP
authors.lastname: Martin
authors.forename: Erica
authors.initials: E
authors.lastname: Scappini
authors.forename: Graeme K
authors.initials: GK
authors.lastname: Carnegie
authors.forename: John P
authors.initials: JP
authors.lastname: O'Bryan
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000378:metabolism; D057809:HEK293 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D005810:Multigene Family; D009422:Nervous System Diseases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011485:Protein Binding; D060066:Protein Interaction Maps; D055503:Protein Multimerization; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D010716:Phosphatidylinositols; C115919:intersectin 1; D020794:Receptor Protein-Tyrosine Kinases; D020558:GTP Phosphohydrolases