Alternative splicing affecting the SH3A domain controls the binding properties of intersectin 1 in neurons

Tsyba, L. O.; Gryaznova, T. A.; Dergai, Oleksandr; Dergai, Mykola; Skrypkina, Inessa; Kropyvko, S. V.; Boldyryev, Oleksiy; Nikolaienko, Oleksii; Novokhatska, Olga; Rynditch, A. V.

doi:10.1016/j.bbrc.2008.05.156

Cited by 34 publications

(36 citation statements)

References 21 publications

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“…The brain-enriched ITSN1-L isoform that has GEF activity toward Cdc42 GTPase was shown to be involved in dendritic spine morphogenesis (Nishimura et al, 2006;Thomas et al, 2009). Our previous results demonstrated that neuron-specific inclusion of exon 20 changes the binding properties of the SH3A domain, shifting its binding specificity from the signalling proteins Sos1 and Cbl to the cytoskeleton regulatory protein CdGAP and the endocytic proteins dynamin 1 and synaptojanin 1 (Tsyba et al, 2008). Skipping of the SH3C domain of ITSN1 or the SH3D domain of ITSN2 could change the interaction interfaces for certain ITSN protein partners or even abolish the interaction.…”

Section: Structure Of Itsn Family Proteinsmentioning

confidence: 98%

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Intersectin multidomain adaptor proteins: Regulation of functional diversity

Tsyba

Nikolaienko

Dergai

et al. 2011

Gene

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Section: Structure Of Itsn Family Proteinsmentioning

confidence: 98%

“…ITSN1 transcripts containing exon 20 are neuron-specific and their expression is developmentally regulated (Tsyba et al, 2004;Tsyba et al, 2008). The frequency of the + exon 20 variant of ITSN1 increases during fetal brain development whereas the level of the transcript lacking exon 20 decreases correspondingly.…”

Section: Structure Of Itsn Family Proteinsmentioning

confidence: 99%

Intersectin multidomain adaptor proteins: Regulation of functional diversity

Tsyba

Nikolaienko

Dergai

et al. 2011

Gene

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“…For example, a microexon in the SH3 domain of the Down syndrome-associated gene Itsn1, which we show here is strongly regulated by nSR100 (Supplemental Fig. S5), promotes interactions with multiple partners (Tsyba et al 2008). A recent report demonstrated that an nSR100-regulated microexon in the Zfyve27 transcript (Fig.…”

Section: Functional Impact Of Nsr100-regulated Microexonsmentioning

confidence: 99%

Essential roles for the splicing regulator nSR100/SRRM4 during nervous system development

et al. 2015

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Alternative splicing (AS) generates vast transcriptomic complexity in the vertebrate nervous system. However, the extent to which trans-acting splicing regulators and their target AS regulatory networks contribute to nervous system development is not well understood. To address these questions, we generated mice lacking the vertebrateand neural-specific Ser/Arg repeat-related protein of 100 kDa (nSR100/SRRM4). Loss of nSR100 impairs development of the central and peripheral nervous systems in part by disrupting neurite outgrowth, cortical layering in the forebrain, and axon guidance in the corpus callosum. Accompanying these developmental defects are widespread changes in AS that primarily result in shifts to nonneural patterns for different classes of splicing events. The main component of the altered AS program comprises 3-to 27-nucleotide (nt) neural microexons, an emerging class of highly conserved AS events associated with the regulation of protein interaction networks in developing neurons and neurological disorders. Remarkably, inclusion of a 6-nt, nSR100-activated microexon in Unc13b transcripts is sufficient to rescue a neuritogenesis defect in nSR100 mutant primary neurons. These results thus reveal critical in vivo neurodevelopmental functions of nSR100 and further link these functions to a conserved program of neuronal microexon splicing.

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“…Previously we described two splicing events affecting exons 6 and 20 of the ITSN1 pre-mRNA: i) inclusion of exon 6′ instead of 6 results in deletion of 37 amino acids between the EH1 and EH2 domains (Tsyba et al, 2004); ii) neuron-specific inclusion of exon 20 that leads to a modification in the structure and ligand specificity of the SH3A domain (Dergai et al, 2010;Tsyba et al, 2008).…”

Section: Itsn1 Isoform With Alternative 3′-end Is Specific Of Placentmentioning

confidence: 99%

“…All PCR-generated DNA fragments were sequenced to confirm fidelity. The constructs expressing the GST fused SH3A domain of ITSN1 and the SH3 domain of amhiphysin 1 were described previously (Dergai et al, 2010;Tsyba et al, 2008).…”

Section: Expression Constructsmentioning

confidence: 99%