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. 2013 Aug 27:4:109.
doi: 10.3389/fendo.2013.00109. eCollection 2013.

Intersectin: The Crossroad between Vesicle Exocytosis and Endocytosis

Olga Gubar  1 , Dmytro Morderer, Lyudmila Tsyba, Pauline Croisé, Sébastien Houy, Stéphane Ory, Stéphane Gasman, Alla Rynditch
Affiliations

Intersectin: The Crossroad between Vesicle Exocytosis and Endocytosis

Olga Gubar et al. Front Endocrinol (Lausanne). .

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.

Keywords: Cdc42; endocytosis; exocytosis; intersectin; neuroendocrine cells; neurons; scaffold.

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Figures

Figure 1
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.
Figure 2
Figure 2
Hypothetical model of ITSN1 coupling exo- and endocytosis in neuroendocrine cells. SNAP-25 recruits ITSN1-L to the SNARE complex (VAMP2, SNAP-25, syntaxin 1) at the exocytic sites where ITSN1-L facilitates regulated exocytosis by activating Cdc42. Immediately after vesicle fusion and hormone release, ITSN1 promotes clathrin-mediated endocytosis of the granule membrane via AP2, and facilitates later stages of endocytosis together with dynamin and synaptojanin. ITSN1 then stays in the vesicle cluster (probably with dynamin) to be recruited back to the membrane for the next release cycle. ITSN1, total ITSN1(both short and long isoforms); ITSN1-L, long isoform of ITSN1.
See this image and copyright information in PMC

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