University of Illinois at Chicago
journal.pone.0036023.pdf (1.77 MB)

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

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posted on 2013-11-22, 00:00 authored by Katy A. Wong, Jessica Wilson, Angela Russo, Li Wang, Mustafa Nazir Okur, Xuerong Wang, Negin P. Martin, Erica Scappini, Graeme K. Carnegie, John P. O’Bryan
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.


KAW was supported by a grant from the Foundation Jerome Lejeune, and LW and GKC were supported by an American Heart Association grant (11SDG5230003). These studies were supported by funds from the intramural research program of the National Institutes of Health (JPO) and by grants to JPO from the National Institutes of Health (HL090651), Department of Defense (PR080428), the Foundation Jerome Lejeune, and the St. Baldrick’s Foundation.


Publisher Statement

The original version is available through Public Library of Science at DOI: 10.1371/journal.pone.0036023. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.


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