Intersectin (ITSN) Family of Scaffolds Function as Molecular Hubs in Protein Interaction Networks
Published Date:Apr 27 2012
Source:PLoS One. 2012; 7(4).
Keywords:Adaptor Proteins, Vesicular Transport
High-Throughput Screening Assays
Nervous System Diseases
Protein Interaction Maps
Receptor Protein-Tyrosine Kinases
Two-Hybrid System Techniques
Pubmed Central ID:PMC3338775
Funding:HL090651/HL/NHLBI NIH HHS/United States
PR080428/PR/OCPHP CDC HHS/United States
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.
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