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


Eps15 represents the prototype of a family of evolutionarily conserved proteins that are characterized by the presence of the EH domain, a protein–protein interaction module1,2, and that are involved in many aspects of intracellular vesicular sorting3. Although biochemical and functional studies have implicated Eps15 in endocytosis4,5, its function in the endocytic machinery remains unclear. Here we show that the Caenorhabditis elegans gene, zk1248.3 (ehs-1), is the orthologue of Eps15 in nematodes, and that its product, EHS-1, localizes to synaptic-rich regions. ehs-1-impaired worms showed 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, which express a mutant form of dynamin and display a temperature-sensitive locomotion defect6, resulted in a worsening of the dyn-1 phenotype and uncoordination at the permissive temperature. Thus, ehs-1 and dyn-1 interact genetically. 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.

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Figure 1: Characterization of the ehs-1 locus and the EHS-1 protein.
Figure 2: A temperature-sensitive locomotion defect in EHS-1-impaired worms.
Figure 3: Depletion of synaptic vesicles in EHS-1-impaired worms.
Figure 4: Interaction between Eps15 and dynamin.

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We thank F. Graziani and S. Confalonieri for discussions; the Caenorhabditis Genetic Center for providing strains; and A. Fire and Y. Kohara for reagents. This work was supported by Associazione Italiana Ricerca sul Cancro (P.B. and P.P.D.F.), the Telethon Foundation (P.P.D.F., C.T. and P.B.), Ministero dell' Universita'e della Ricerca Scientifica e Tecnologica (C.T.), Consiglio Nazionale delle Ricerche (Target project Biotechnology; C.T. and P.P.D.F.) and the NIH (P.D.C).

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Correspondence to Pier Paolo Di Fiore.

Supplementary information

Supplementary figures and methods

Figure S1 Comparison of human Eps15 and EHS-1. (PDF 2784 kb)

Figure S2 The COIL region of the EHS-1 is necessary for its transport to synapses.

Figure S3 Localisation of EHS-1 in various unc mutants.

Figure S4 Further characterisation of the anti-EHS-1 antibody.

Figure S5 ehs-1 interference in the dyn-1(ky51) genetic background.

Figure S6 Dynamin purity.

Supplementary Methods Engineering of constructs and oligonucleotides.

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