The promotion of gonadal cell divisions by the Caenorhabditis elegans TRPM cation channel GON-2 is antagonized by GEM-4 copine.
The initiation of postembryonic cell divisions by the gonadal precursors of C. elegans requires the activity of gon-2. gon-2 encodes a predicted cation channel (GON-2) of the TRPM subfamily of TRP proteins and is likely to mediate the influx of Ca(2+) and/or Mg(2+). We report here that mutations in gem-4 (gon-2 extragenic modifier) are capable of suppressing loss-of-function alleles of gon-2. gem-4 encodes a member of the copine family of Ca(2+)-dependent phosphatidylserine binding proteins. Overall, our data indicate that GEM-4 antagonizes GON-2. This antagonism could be mediated by a direct inhibition of GON-2 by GEM-4, since both proteins are predicted to be localized to the plasma membrane. Alternatively, GEM-4 could affect GON-2 activity levels by either promoting endocytosis or inhibiting exocytosis of vesicles that carry GON-2. It is also possible that GEM-4 and GON-2 act in parallel to each other. Mutation of gem-4 does not suppress the gonadal defects produced by inactivation of gon-4, suggesting that gon-4 either acts downstream of gem-4 and gon-2 or acts in a parallel regulatory pathway.
Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA.
Diane L
DL
Church
Eric J
EJ
Lambie
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002874:Chromosome Mapping; D006066:Gonads / Q000502:physiology*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D010718:Phosphatidylserines / Q000378:metabolism; D034622:RNA Interference
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C487577:GEM-4 protein, C elegans; C487576:GON-2 protein, C elegans; D007473:Ion Channels; D010718:Phosphatidylserines; C110203:copine