We are interested in studying the molecular mechanisms that regulate active zone formation. In a forward genetic screen utilizing an active zone GFP marker hpIs3 (Punc-25- SYD-2::GFP) (Yeh et al., J of Neurosci. 25(15):3833-41, 2005), we identified
hp102, an allele of
unc-77/nca-1, that is defective in hpIs3 distribution. The hpIs3 marker is clustered with gaps along the nerve cords of
hp102 mutants. Also,
hp102 animals display loopy forward and coiler backward movements.
hp102 is a gain of function allele of
nca-1/unc-77 (Yeh et al., 2005 International Worm Meeting 629A), which encodes the alpha-subunit of a putative novel calcium channel (Hamming et al., 2003 International C. elegans meeting 9). We determined that NCA-1 is expressed in many sensory neurons and motorneurons by immunofluorescent staining. Recently we found that
hp102 is suppressed by mutations in
unc-79 and
unc-80, both of which encode large uncharacterized proteins that have been shown to affect volatile anesthetic sensitivity (Morgan et al., PNAS 87:2965-2969, 1990). We observed that
nca-1 expression/localization disappears or decreases in
unc-79 and
unc-80 mutants, suggesting that UNC-80 is required for NCA-1 expression/localization. Our preliminary data suggests that
unc-80 is also expressed in many motorneurons. We hypothesize that the
nca-1/unc-77 calcium/sodium channel, regulated by
unc-79/unc-80, is required for the incorporation of active zone proteins and the activity of the synapse. Current progress will be presented. (* Both authors contributed equally to this work.)