Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated pits

Department of Functional Genomics, Institute of Molecular Biology and Genetics, NASU, 150 Zabolotnogo Street, 03680 Kyiv, Ukraine.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 10/2010; 402(2):408-13. DOI: 10.1016/j.bbrc.2010.10.045
Source: PubMed


Intersectin 1 (ITSN1) is an evolutionarily conserved adaptor protein involved in clathrin-mediated endocytosis, cellular signaling and cytoskeleton rearrangement. ITSN1 gene is located on human chromosome 21 in Down syndrome critical region. Several studies confirmed role of ITSN1 in Down syndrome phenotype. Here we report the identification of novel interconnections in the interaction network of this endocytic adaptor. We show that the membrane-deforming protein SGIP1 (Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1) and the signaling adaptor Reps1 (RalBP associated Eps15-homology domain protein) interact with ITSN1 in vivo. Both interactions are mediated by the SH3 domains of ITSN1 and proline-rich motifs of protein partners. Moreover complexes comprising SGIP1, Reps1 and ITSN1 have been identified. We also identified new interactions between SGIP1, Reps1 and the BAR (Bin/amphiphysin/Rvs) domain-containing protein amphiphysin 1. Immunofluorescent data have demonstrated colocalization of ITSN1 with the newly identified protein partners in clathrin-coated pits. These findings expand the role of ITSN1 as a scaffolding molecule bringing together components of endocytic complexes.

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    ABSTRACT: Adaptor/scaffold proteins serve as platforms for the assembly of multiprotein complexes and regulate the efficiency and specificity of signalling cascades. Intersectins (ITSNs) are an evolutionarily conserved adaptor protein family engaged in endo- and exocytosis, actin cytoskeleton rearrangement and signal transduction. This review summarizes recent advances in the function of ITSNs in neuronal and non-neuronal cells, the role of alternative splicing and alternative transcription in regulating the structural and functional diversity of ITSNs, their expression patterns in different tissues and during development, their interactions with proteins, as well as the potential relevance of ITSNs for neurodegenerative diseases and cancer. The diversity of mechanisms in the regulation of ITSN expression and specificity in different cells emphasizes the important role of ITSN proteins in vesicle trafficking and signalling.
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