Intersectin (ITSN) Family of Scaffolds Function as Molecular Hubs in Protein Interaction Networks

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Wong, Katy A. ; Wilson, Jessica ; Russo, Angela ; Wang, Li ; Okur, Mustafa Nazir ; Wang, Xuerong ; Martin, Negin P. ; Scappini, Erica ; Carnegie, Graeme K. ; O'Bryan, John P.
• Description:
  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.
• Subjects:
  Adaptor Proteins, Vesicular Transport Animals Cercopithecus Aethiops COS Cells Endocytosis GTP Phosphohydrolases HEK293 Cells High-Throughput Screening Assays Humans Multigene Family Nervous System Diseases Phosphatidylinositols Protein Binding Protein Interaction Maps Protein Multimerization Receptor Protein-Tyrosine Kinases Signal Transduction Two-Hybrid System Techniques

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• Source:
  PLoS One. 2012; 7(4).
• Pubmed ID:
  22558309
• Pubmed Central ID:
  PMC3338775
• Document Type:
  Journal Article
• Funding:
  HL090651/HL/NHLBI NIH HHS/United States ; PR080428/PR/OCPHP CDC HHS/United States
• Volume:
  7
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:4700c73552fd12bee0f9de5c907de7855846421cb6189e808b8e137eb4629303
• Download URL:
  https://stacks.cdc.gov/view/cdc/22749/cdc_22749_DS1.pdf
• File Type:
  [PDF - 1.77 MB ]