| Two novel multidomain genes were cloned and termed Ese1/Intersectin1 and Ese2/Intersectin2. These proteins contain two N-terminal EH domains, a central coiled-coil domain and five SH3 domains. Each gene has an alternatively spliced isoform called Ese1L/Intersectin1L and Ese2L/Intersectin2L respectively, which have Dbl, PH and C2 domains on a C-terminal extension to the above mentioned domains. For the remainder of this document, Ese/Intersectin will be referred to as Ese. The Ese proteins are novel adapters or scaffolds belonging to the family of EH-domain containing proteins. We have identified many protein partners that bind to various domains of Ese. Ese1/2 are implicated in internalization steps of Clathrin-mediated and Caveolin-mediated endocytosis. We report here that Ese1S binds endosomal sorting proteins, Tsg101, Alix and Cbl-b in vivo and overexpression of Ese1S can attract EGF-containing vesicles, suggesting a novel role in regulating sorting and recycling events. Using genetic approaches in mice, we have uncovered a role for Ese1 in brain and neurovascular patterning, seizure control and developmental growth. |
