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

TY - JOUR

T1 - The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling.

AU - Salcini, A E

AU - Hilliard, M A

AU - Croce, A

AU - Arbucci, S

AU - Luzzi, P

AU - Tacchetti, C

AU - Daniell, L

AU - De Camilli, P

AU - Pelicci, P G

AU - Di Fiore, P P

AU - Bazzicalupo, P

N1 - Keywords: Aldicarb; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Calcium-Binding Proteins; Dynamins; Fluorescent Antibody Technique; GTP Phosphohydrolases; Ganglia, Invertebrate; Gene Deletion; Genes, Reporter; Insecticides; Microscopy, Electron; Molecular Sequence Data; Movement Disorders; Mutation; Nerve Tissue Proteins; Nervous System; Phenotype; Phosphoproteins; Protein Transport; Sequence Homology, Nucleic Acid; Synaptic Vesicles; Temperature

PY - 2001

Y1 - 2001

N2 - 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 module, and that are involved in many aspects of intracellular vesicular sorting. Although biochemical and functional studies have implicated Eps15 in endocytosis, 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 defect, 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.

AB - 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 module, and that are involved in many aspects of intracellular vesicular sorting. Although biochemical and functional studies have implicated Eps15 in endocytosis, 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 defect, 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.

U2 - 10.1038/35087075

DO - 10.1038/35087075

M3 - Journal article

C2 - 11483962

SN - 1465-7392

VL - 3

SP - 755

EP - 760

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 8

ER -