The C.elegans gene
ehs-1 (
zk1248.3) codes for the homologue of mammalian Eps15, a protein involved in endocytic processes. The binding to AP-2 complex, its localisation at the rim of coated pits, the presence in the N-terminal part of three EH domains, a protein-protein interaction domain shared with yeast proteins involved in endocytosis, the inhibition of receptor internalisation by dominant negative mutants of Eps15, are the prominent features of the mammalian protein. We will show that EHS-1 retains the biochemical properties of Eps15 and, as its mammalian counterpart, it is involved in a specializated endocytic process. Immunofluorescence analysis with specific antibodies in wild type worms reveals that EHS-1 localizes exclusively to synaptic-rich regions. Its mislocalisation in
unc-104 mutant worms indicates that EHS-1 is transported to synapses by the same machinery used by synaptic vesicles. Reporter analysis confirms that
ehs-1 is expressed in most or all neurons,beginning in late embryos and that expression in other cells is absent or below detection. Transformation of worms with constructs producing full length or truncated forms of EHS-1 fused to GFP have helped identify the domains of the protein necessary for its transport to the synapses. RNA interference and transformation with a truncated form of EHS-1 producing a dominant negative effect, result in a temperature-sensitive, reversible uncoordinated phenotype, reminiscent of that of
dyn-1 mutants. We will discuss data indicating that
ehs-1 acts in the synaptic vesicle recycling pathway and that it interacts genetically with
dyn-1 .