title: Intersectin adaptor proteins are associated with actin-regulating protein WIP in invadopodia.
abstract: Invasive cancer cells form actin-rich membrane protrusions called invadopodia that degrade extracellular matrix and facilitate cell invasion and metastasis. WIP (WASP-interacting protein) together with N-WASP (neural Wiskott-Aldrich syndrome protein) are localized in invadopodia and play a crucial role in their formation. Here we show that WIP interacts with endocytic adaptor proteins of the intersectin (ITSN) family, ITSN1 and ITSN2. The interaction is mediated by the SH3 domains of ITSNs and the middle part of the WIP proline-rich motifs. We have also demonstrated that ITSN1, WIP and N-WASP can form a complex in cells. Endogenous ITSN1 and ITSN2 are located in invasive protrusions of MDA-MB-231 breast cancer cell line. Moreover, data from immunofluorescent analysis revealed co-localization of ITSN1 and WIP at sites of invadopodia formation and in clathrin-coated pits. Together, these findings provide insights into the molecular mechanisms of invadopodia formation and identify ITSNs as scaffold proteins involved in this process.
authors: Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, Kyiv 03680, Ukraine. Electronic address: t.griaznova@gmail.com.
authors: Tetyana
authors: T
authors: Gryaznova
authors: Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, Kyiv 03680, Ukraine.
authors: Sergii
authors: S
authors: Kropyvko
authors: Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, Kyiv 03680, Ukraine.
authors: Mariia
authors: M
authors: Burdyniuk
authors: Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, Kyiv 03680, Ukraine.
authors: Olga
authors: O
authors: Gubar
authors: Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, Kyiv 03680, Ukraine.
authors: Valentyna
authors: V
authors: Kryklyva
authors: Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, Kyiv 03680, Ukraine.
authors: Liudmyla
authors: L
authors: Tsyba
authors: Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, Kyiv 03680, Ukraine.
authors: Alla
authors: A
authors: Rynditch
mesh_terms: D000199:Actins / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D000069261:Podosomes / Q000378:metabolism*; D011485:Protein Binding; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D000199:Actins; D033942:Adaptor Proteins, Vesicular Transport; D003598:Cytoskeletal Proteins; C485568:ITSN1 protein, human; C509776:ITSN2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C109903:WIPF1 protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
keywords: Actin cytoskeleton; Intersectin; Invadopodia; N-WASP; WIP