Interactions between innexins UNC-7 and UNC-9 mediate electrical synapse specificity in the Caenorhabditis elegans locomotory nervous system.
BACKGROUND
Approximately 10% of Caenorhabditis elegans nervous system synapses are electrical, that is, gap junctions composed of innexins. The locomotory nervous system consists of several pairs of interneurons and three major classes of motor neurons, all with stereotypical patterns of connectivity that include gap junctions. Mutations in the two innexin genes unc-7 and unc-9 result in identical uncoordinated movement phenotypes, and their respective gene products were investigated for their contribution to electrical synapse connectivity.


RESULTS
unc-7 encodes three innexin isoforms. Two of these, UNC-7S and UNC-7SR, are functionally equivalent and play an essential role in coordinated locomotion. UNC-7S and UNC-7SR are widely expressed and co-localize extensively with green fluorescent protein-tagged innexin UNC-9 in the ventral and dorsal nerve cords. A subset of UNC-7S/SR expression visualizes gap junctions formed between the AVB forward command interneurons and their B class motor neuron partners. Experiments indicate that expression of UNC-7S/SR in AVB and expression of UNC-9 in B motor neurons is necessary for these gap junctions to form. In Xenopus oocyte pairs, both UNC-7S and UNC-9 form homomeric gap junctions, and together they form heterotypic channels. Xenopus oocyte studies and co-localization studies in C. elegans suggest that UNC-7S and UNC-9 do not heteromerize in the same hemichannel, leading to the model that hemichannels in AVB:B motor neuron gap junctions are homomeric and heterotypic.


CONCLUSIONS
UNC-7S and UNC-9 are widely expressed and contribute to a large number of the gap junctions identified in the locomotory nervous system. Proper AVB:B gap junction formation requires UNC-7S expression in AVB interneurons and UNC-9 expression in B motor neurons. More broadly, this illustrates that innexin identity is critical for electrical synapse specificity, but differential (compartmentalized) innexin expression cannot account for all of the specificity seen in C. elegans, and other factors must influence the determination of synaptic partners.
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55406, USA. stari001@umn.edu
Todd A
TA
Starich
Ji
J
Xu
I Martha
IM
Skerrett
Bruce J
BJ
Nicholson
Jocelyn E
JE
Shaw
D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D001703:Biophysics; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000166:cytology*; D004558:Electric Stimulation; D054351:Electrical Synapses / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D008124:Locomotion / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D009865:Oocytes; D018408:Patch-Clamp Techniques; D014162:Transfection / Q000379:methods; D014981:Xenopus
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C094444:Unc-7 protein, C elegans; C109201:Unc-9 protein, C elegans; D049452:Green Fluorescent Proteins