Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated pits.
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.
Dergai
Oleksandr
O
Department of Functional Genomics, Institute of Molecular Biology and Genetics, NASU, 150 Zabolotnogo Street, 03680 Kyiv, Ukraine. o.dergai@gmail.com
Novokhatska
Olga
O
Dergai
Mykola
M
Skrypkina
Inessa
I
Tsyba
Liudmyla
L
Moreau
Jacques
J
Rynditch
Alla
A
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism*; D004705:Endocytosis; D006801:Humans; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C484665:REPS1 protein, human; C523897:SGIP1 protein, human; C115919:intersectin 1; C075637:amphiphysin