journal.pone.0036023.pdf (1.77 MB)
Download fileIntersectin (ITSN) Family of Scaffolds Function as Molecular Hubs in Protein Interaction Networks
journal contribution
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’BryanMembers 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.