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 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.
Salcini
A E
AE
Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy.
Hilliard
M A
MA
Croce
A
A
Arbucci
S
S
Luzzi
P
P
Tacchetti
C
C
Daniell
L
L
De Camilli
P
P
Pelicci
P G
PG
Di Fiore
P P
PP
Bazzicalupo
P
P
D000448:Aldicarb / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D034281:Dynamins; D005455:Fluorescent Antibody Technique; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D017952:Ganglia, Invertebrate / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D017353:Gene Deletion; D017930:Genes, Reporter / Q000502:physiology; D007306:Insecticides / Q000494:pharmacology; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009069:Movement Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013696:Temperature
D002135:Calcium-Binding Proteins; D007306:Insecticides; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D000448:Aldicarb; D020558:GTP Phosphohydrolases; D034281:Dynamins