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Intersectin: The Crossroad between Vesicle Exocytosis and Endocytosis.

Gubar O, Morderer D, Tsyba L, Croisé P, Houy S, Ory S, Gasman S, Rynditch A - Front Endocrinol (Lausanne) (2013)

Bottom Line: Further investigation demonstrated that ITSN1 is also implicated in several other processes including regulated exocytosis, thereby suggesting a role for ITSN1 in the coupling between exocytosis and endocytosis in excitatory cells.Despite a high degree of conservation amongst orthologs, ITSN function is not so well preserved as they have acquired new properties during evolution.In this review, we will discuss the role of ITSN1 and its orthologs in exo- and endocytosis, in particular in neurons and neuroendocrine cells.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Molecular and Cellular Biology, Institute of Molecular Biology and Genetics , Kyiv , Ukraine ; Department of Functional Genomics, Institute of Molecular Biology and Genetics , Kyiv , Ukraine ; Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique-Unité Propre de Recherche 3212, Université de Strasbourg , Strasbourg , France.

ABSTRACT
Intersectins (ITSNs) are a family of highly conserved proteins with orthologs from nematodes to mammals. In vertebrates, ITSNs are encoded by two genes (itsn1 and itsn2), which act as scaffolds that were initially discovered as proteins involved in endocytosis. Further investigation demonstrated that ITSN1 is also implicated in several other processes including regulated exocytosis, thereby suggesting a role for ITSN1 in the coupling between exocytosis and endocytosis in excitatory cells. Despite a high degree of conservation amongst orthologs, ITSN function is not so well preserved as they have acquired new properties during evolution. In this review, we will discuss the role of ITSN1 and its orthologs in exo- and endocytosis, in particular in neurons and neuroendocrine cells.

No MeSH data available.


ITSN orthologs and domain composition. Schematic representation of the ITSN proteins in different species depicting the position of various functional domains. EH, Eps15 homology domain; SH3, Src homology 3 domain; DH, Dbl homology domain; PH, pleckstrin homology domain; C2, Ca2+-binding domain. Vertebrates usually have two ITSN genes, both of which give rise to two major isoforms.
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Figure 1: ITSN orthologs and domain composition. Schematic representation of the ITSN proteins in different species depicting the position of various functional domains. EH, Eps15 homology domain; SH3, Src homology 3 domain; DH, Dbl homology domain; PH, pleckstrin homology domain; C2, Ca2+-binding domain. Vertebrates usually have two ITSN genes, both of which give rise to two major isoforms.

Mentions: Intersectin is highly conserved in all metazoans examined so far and ITSN orthologs have been found in nematodes (Caenorhabditis elegans) (4), arthropods (Drosophila melanogaster Dap160 – Dynamin-associated protein 160 kDa) (5), fish (Danio rerio) (6), amphibians (Xenopus laevis) (7), and mammals (Mus musculus, Rattus norvegicus, Homo sapiens) (8–10) (Figure 1). ITSN is encoded by one gene in invertebrates. Its molecular organization consists of two N-terminal EH (Eps15 homology) domains followed by a coiled-coil region and four or five SH3 (Src homology 3) domains (5). In vertebrates, two genes encode ITSN proteins (ITSN1 and ITSN2). In addition, ITSNs exist in two main isoforms generated by alternative splicing: a short form (ITSN-S) that harbors the same domain organization as invertebrate ITSN and is ubiquitously expressed and a long form (ITSN-L) which has three additional domains in its C-terminal part [tandem of Dbl (DH) and pleckstrin homology (PH) domains and a C2 domain] (10). This extension has guanine nucleotide exchange factor (GEF) properties for Cdc42 (11), a small GTPase of the Rho family. The ITSN1-L is enriched in neurons (10, 12).


Intersectin: The Crossroad between Vesicle Exocytosis and Endocytosis.

Gubar O, Morderer D, Tsyba L, Croisé P, Houy S, Ory S, Gasman S, Rynditch A - Front Endocrinol (Lausanne) (2013)

ITSN orthologs and domain composition. Schematic representation of the ITSN proteins in different species depicting the position of various functional domains. EH, Eps15 homology domain; SH3, Src homology 3 domain; DH, Dbl homology domain; PH, pleckstrin homology domain; C2, Ca2+-binding domain. Vertebrates usually have two ITSN genes, both of which give rise to two major isoforms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3753573&req=5

Figure 1: ITSN orthologs and domain composition. Schematic representation of the ITSN proteins in different species depicting the position of various functional domains. EH, Eps15 homology domain; SH3, Src homology 3 domain; DH, Dbl homology domain; PH, pleckstrin homology domain; C2, Ca2+-binding domain. Vertebrates usually have two ITSN genes, both of which give rise to two major isoforms.
Mentions: Intersectin is highly conserved in all metazoans examined so far and ITSN orthologs have been found in nematodes (Caenorhabditis elegans) (4), arthropods (Drosophila melanogaster Dap160 – Dynamin-associated protein 160 kDa) (5), fish (Danio rerio) (6), amphibians (Xenopus laevis) (7), and mammals (Mus musculus, Rattus norvegicus, Homo sapiens) (8–10) (Figure 1). ITSN is encoded by one gene in invertebrates. Its molecular organization consists of two N-terminal EH (Eps15 homology) domains followed by a coiled-coil region and four or five SH3 (Src homology 3) domains (5). In vertebrates, two genes encode ITSN proteins (ITSN1 and ITSN2). In addition, ITSNs exist in two main isoforms generated by alternative splicing: a short form (ITSN-S) that harbors the same domain organization as invertebrate ITSN and is ubiquitously expressed and a long form (ITSN-L) which has three additional domains in its C-terminal part [tandem of Dbl (DH) and pleckstrin homology (PH) domains and a C2 domain] (10). This extension has guanine nucleotide exchange factor (GEF) properties for Cdc42 (11), a small GTPase of the Rho family. The ITSN1-L is enriched in neurons (10, 12).

Bottom Line: Further investigation demonstrated that ITSN1 is also implicated in several other processes including regulated exocytosis, thereby suggesting a role for ITSN1 in the coupling between exocytosis and endocytosis in excitatory cells.Despite a high degree of conservation amongst orthologs, ITSN function is not so well preserved as they have acquired new properties during evolution.In this review, we will discuss the role of ITSN1 and its orthologs in exo- and endocytosis, in particular in neurons and neuroendocrine cells.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Molecular and Cellular Biology, Institute of Molecular Biology and Genetics , Kyiv , Ukraine ; Department of Functional Genomics, Institute of Molecular Biology and Genetics , Kyiv , Ukraine ; Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique-Unité Propre de Recherche 3212, Université de Strasbourg , Strasbourg , France.

ABSTRACT
Intersectins (ITSNs) are a family of highly conserved proteins with orthologs from nematodes to mammals. In vertebrates, ITSNs are encoded by two genes (itsn1 and itsn2), which act as scaffolds that were initially discovered as proteins involved in endocytosis. Further investigation demonstrated that ITSN1 is also implicated in several other processes including regulated exocytosis, thereby suggesting a role for ITSN1 in the coupling between exocytosis and endocytosis in excitatory cells. Despite a high degree of conservation amongst orthologs, ITSN function is not so well preserved as they have acquired new properties during evolution. In this review, we will discuss the role of ITSN1 and its orthologs in exo- and endocytosis, in particular in neurons and neuroendocrine cells.

No MeSH data available.