The Eps15 C-elegans homologue EHS-1 is implicated in synaptic vesicle recycling

Eps15 represents the prototype of a family of evolutionarily conserved prot eins that are characterized by the presence of the EH domain, a protein-pro tein interaction module(1,2), and that are involved in many aspects of intr acellular vesicular sorting(3). Although biochemical and functional studies have implicated Eps15 in endocytosis(4,5), its function in the endocytic m achinery remains unclear. Here we show that the Caenorhabditis elegans gene , zk1248.3 (ehs-1), is the orthologue of Eps15 in nematodes, and that its p roduct, EHS-1, localizes to synaptic-rich regions. ehs-l-impaired worms sho wed temperature-dependent depletion of synaptic vesicles and uncoordinated movement. These phenotypes could be correlated with a presynaptic defect in neurotransmission. Impairment of EHS-1 function in dyn-1(ky51) worms, whic h express a mutant form of dynamin and display a temperature-sensitive loco motion defects, resulted in a worsening of the dyn-1 phenotype and uncoordi nation at the permissive temperature. Thus, ehs-1 and dyn-1 interact geneti cally. Moreover, mammalian Eps15 and dynamin protein were shown to interact in vivo. Taken together, our results indicate that EHS-1 acts in synaptic vesicle recycling and that its function might be linked to that of dynamin.