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Intersectin 1 (ITSN1) is an evolutionarily conserved adaptor protein that functions in clathrin-mediated endocytosis, cell signalling and cytoskeleton rearrangements. The ITSN1 gene encodes two main isoforms: a short form (ITSN1-s), which is ubiquitously expressed and consists of two Eps15 homology (EH) domains and five Src homology 3 (SH3) domains, and a long form (ITSN1-l), which is predominantly expressed in the brain and contains three additional domains, a Dbl homology (DH) domain, a Pleckstrin homology (PH) domain and a C2 domain. Using computational analysis of the EST database and 3' RACE we determined the length of the 3' untranslated region of ITSN1-l and demonstrated that the polyadenylation site is located 11,559 nt downstream of the stop codon of the ITSN1-l mRNA. Recently, additional splicing events affecting ITSN1 transcripts were reported, but full-length transcriptional isoforms with different combinations of alternatively spliced exons remained unknown. Here we report the identification of fifteen novel transcriptional isoforms of the human ITSN1 gene with full-length coding sequences that are the result of different combinations of the alternatively spliced exons 5, 6/6', 20, 23, 25, 26, 26a and 35. The isoforms identified differ in domain organization and expression level in different tissues and more likely contribute to the modulation of many complex protein interactions in which ITSN1 participates.

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Adaptor/scaffold proteins of the intersectin (ITSN) family are important components of endocytic and signalling complexes. They coordinate trafficking events with actin cytoskeleton rearrangements and modulate the activity of a variety of signalling pathways. In this review, we present our results as a part of recent findings on the function of ITSNs, the role of alternative splicing in the generation of ITSN1 diversity and the potential relevance of ITSNs for neurodegenerative diseases, cancer

TKS4 scaffold protein is involved in formation of invadopodia, production of reactive oxygen species (ROS) by tumor cells and other cellular processes. Aim. To identify new TKS4 partners involved in the actin cytoskeleton rearrangements and endo-/exocytosis. Methods. The GST pull-down assay was used to identify the interaction. Results. We revealed that TKS4 SH3 domains interacted with the actin cytoskeleton reorganization proteins N-WASP and CR16, as well as with DNM2, SYNJ1 and OPHN1 which are involved in endo-/ exocytosis. We also tested the WIP, WIRE, SHIP2, RhoU, RhoV and NUMB proteins, but their interaction with the SH3 domains of TKS4 was not found. Conclusions. The SH3 domains of TKS4 interact with N-WASP, DNM2, SYNJ1, OPHN1 and weakly with CR16 in vitro. K e y w o r d s: TKS4, adaptor/scaffold proteins, actin cytoskeleton, endo-/exocytosis. К л юч е в ы е с л ов а: TKS4; адапторные/скаффолдные белки; актиновий цитоскелет ; эндо-/экзоцитоз