Intersectin 2 nucleotide exchange factor regulates Cdc42 activity during Xenopus early development

Novokhatska, Olga; Dergai, Mykola; Houssin, Nathalie; Tsyba, L. O.; Moreau, Jacques; Rynditch, A. V.

doi:10.1016/j.bbrc.2011.04.081

Cited by 13 publications

(13 citation statements)

References 22 publications

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“…The data on ITSN2 are limited, and so far only a few of its protein partners were characterized [2], [15]–[17]. Most of the known ITSN2 functions are linked to the regulation of activity of the small GTPase Cdc42 in various cell types by its long splice variant that possesses a GDP/GTP-exchange domain [15], [18]–[20]. The ITSN1 long splice variant is neuron-enriched and participates in dendritic spine development and synaptic vesicle trafficking [21]–[23].…”

Section: Introductionmentioning

confidence: 99%

Adaptor Proteins Intersectin 1 and 2 Bind Similar Proline-Rich Ligands but Are Differentially Recognized by SH2 Domain-Containing Proteins

et al. 2013

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BackgroundScaffolding proteins of the intersectin (ITSN) family, ITSN1 and ITSN2, are crucial for the initiation stage of clathrin-mediated endocytosis. These proteins are closely related but have implications in distinct pathologies. To determine how these proteins could be separated in certain cell pathways we performed a comparative study of ITSNs.Methodology/Principal FindingsWe have shown that endogenous ITSN1 and ITSN2 colocalize and form a complex in cells. A structural comparison of five SH3 domains, which mediated most ITSNs protein-protein interactions, demonstrated a similarity of their ligand-binding sites. We showed that the SH3 domains of ITSN2 bound well-established interactors of ITSN1 as well as newly identified ITSNs protein partners. A search for a novel interacting interface revealed multiple tyrosines that could be phosphorylated in ITSN2. Phosphorylation of ITSN2 isoforms but not ITSN1 short isoform was observed in various cell lines. EGF stimulation of HeLa cells enhanced tyrosine phosphorylation of ITSN2 isoforms and enabled their recognition by the SH2 domains of the Fyn, Fgr and Abl1 kinases, the regulatory subunit of PI3K, the adaptor proteins Grb2 and Crk, and phospholipase C gamma. The SH2 domains mentioned were unable to bind ITSN1 short isoform.Conclusions/SignificanceOur results indicate that during evolution of vertebrates ITSN2 acquired a novel protein-interaction interface that allows its specific recognition by the SH2 domains of signaling proteins. We propose that these data could be important to understand the functional diversity of paralogous ITSN proteins.

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Section: Introductionmentioning

confidence: 99%

Adaptor Proteins Intersectin 1 and 2 Bind Similar Proline-Rich Ligands but Are Differentially Recognized by SH2 Domain-Containing Proteins

et al. 2013

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“…ITSN2-L regulates Cdc42 activity and actin cytoskeleton dynamics during early Xenopus development [45]. In Drosophila , Dap160 is enriched in plasma membrane fractions, and localized to areas adjacent to the active zone [34].…”

Section: Functionmentioning

confidence: 99%

Intersectin scaffold proteins and their role in cell signaling and endocytosis

Herrero-Garcia

O’Bryan

2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Intersectins (ITSNs) are a family of multi-domain proteins involved in regulation of diverse cellular pathways. These scaffold proteins are well known for regulating endocytosis but also play important roles in cell signaling pathways including kinase regulation and Ras activation. ITSNs participate in several human cancers, such as neuroblastomas and glioblastomas, while its downregulation is associated with lung injury. Alterations in ITSN expression have been found in neurodegenerative diseases such as Down Syndrome and Alzheimer’s disease. Binding proteins for ITSNs include endocytic regulatory factors, cytoskeleton related proteins (i.e. actin or dynamin), signaling proteins as well as herpes virus proteins. This review will summarize recent studies on ITSNs, highlighting the importance of these scaffold proteins in the aforementioned processes.

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“…Novokhatska and colleagues examined the function of ITSN2-L in embryonic development of Xenopus laevis [20]. ITSN2-L transcripts were detected in the two-cell stage through the tadpole stage.…”

Section: A Growing Number Of Itsn-regulated Cell Signaling Pathwaysmentioning

confidence: 99%

Emerging Roles for Intersectin (ITSN) in Regulating Signaling and Disease Pathways

Hunter

Russo

O’Bryan

2013

IJMS

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Intersectins (ITSNs) represent a family of multi-domain adaptor proteins that regulate endocytosis and cell signaling. ITSN genes are highly conserved and present in all metazoan genomes examined thus far. Lower eukaryotes have only one ITSN gene, whereas higher eukaryotes have two ITSN genes. ITSN was first identified as an endocytic scaffold protein, and numerous studies reveal a conserved role for ITSN in endocytosis. Subsequently, ITSNs were found to regulate multiple signaling pathways including receptor tyrosine kinases (RTKs), GTPases, and phosphatidylinositol 3-kinase Class 2beta (PI3KC2β). ITSN has also been implicated in diseases such as Down Syndrome (DS), Alzheimer Disease (AD), and other neurodegenerative disorders. This review summarizes the evolutionary conservation of ITSN, the latest research on the role of ITSN in endocytosis, the emerging roles of ITSN in regulating cell signaling pathways, and the involvement of ITSN in human diseases such as DS, AD, and cancer.

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Intersectin 2 nucleotide exchange factor regulates Cdc42 activity during Xenopus early development

Cited by 13 publications

References 22 publications

Adaptor Proteins Intersectin 1 and 2 Bind Similar Proline-Rich Ligands but Are Differentially Recognized by SH2 Domain-Containing Proteins

Adaptor Proteins Intersectin 1 and 2 Bind Similar Proline-Rich Ligands but Are Differentially Recognized by SH2 Domain-Containing Proteins

Intersectin scaffold proteins and their role in cell signaling and endocytosis

Emerging Roles for Intersectin (ITSN) in Regulating Signaling and Disease Pathways

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