UNC-11, a Caenorhabditis elegans AP180 homologue, regulates the size and protein composition of synaptic vesicles.
The unc-11 gene of Caenorhabditis elegans encodes multiple isoforms of a protein homologous to the mammalian brain-specific clathrin-adaptor protein AP180. The UNC-11 protein is expressed at high levels in the nervous system and at lower levels in other tissues. In neurons, UNC-11 is enriched at presynaptic terminals but is also present in cell bodies. unc-11 mutants are defective in two aspects of synaptic vesicle biogenesis. First, the SNARE protein synaptobrevin is mislocalized, no longer being exclusively localized to synaptic vesicles. The reduction of synaptobrevin at synaptic vesicles is the probable cause of the reduced neurotransmitter release observed in these mutants. Second, unc-11 mutants accumulate large vesicles at synapses. We propose that the UNC-11 protein mediates two functions during synaptic vesicle biogenesis: it recruits synaptobrevin to synaptic vesicle membranes and it regulates the size of the budded vesicle during clathrin coat assembly.
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. nonetm@thalamus.wustl.edu
M L
ML
Nonet
A M
AM
Holgado
F
F
Brewer
C J
CJ
Serpe
B A
BA
Norbeck
J
J
Holleran
L
L
Wei
E
E
Hartwieg
E M
EM
Jorgensen
A
A
Alfonso
D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D002966:Clathrin / Q000096:biosynthesis; D004705:Endocytosis; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism*; D006720:Homozygote; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D034041:Monomeric Clathrin Assembly Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics; D020033:Protein Isoforms; D050683:R-SNARE Proteins; D017386:Sequence Homology, Amino Acid; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D014714:Vertebrates
D033942:Adaptor Proteins, Vesicular Transport; D029742:Caenorhabditis elegans Proteins; D002966:Clathrin; D015801:Helminth Proteins; D008565:Membrane Proteins; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010750:Phosphoproteins; D020033:Protein Isoforms; D050683:R-SNARE Proteins; C439023:clathrin assembly protein AP180; C120753:unc-11 protein, C elegans