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Structural diversity and differential expression of novel human intersectin 1 isoforms

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Abstract

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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Acknowledgments

We thank Dr. O. Boldyryev for the isolation of mouse neurons and Prof. A.-L. Haenni for helpful discussions and comments on the manuscript. This work was supported by an INTAS Grant (No. 05-1000004-7762).

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Authors and Affiliations

  1. Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, 03680, Kyiv, Ukraine

    Sergii Kropyvko, Dmytro Gerasymchuk, Inessa Skrypkina, Mykola Dergai, Oleksandr Dergai, Oleksii Nikolaienko, Alla Rynditch & Liudmyla Tsyba

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  1. Sergii Kropyvko
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  2. Dmytro Gerasymchuk
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  5. Oleksandr Dergai
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  6. Oleksii Nikolaienko
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  8. Liudmyla Tsyba
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Correspondence to Liudmyla Tsyba.

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Kropyvko, S., Gerasymchuk, D., Skrypkina, I. et al. Structural diversity and differential expression of novel human intersectin 1 isoforms. Mol Biol Rep 37, 2789–2796 (2010). https://doi.org/10.1007/s11033-009-9824-8

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  • DOI: https://doi.org/10.1007/s11033-009-9824-8

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