The Caenorhabditis elegans unc-49 locus encodes multiple subunits of a heteromultimeric GABA receptor.
Ionotropic GABA receptors generally require the products of three subunit genes. By contrast, the GABA receptor needed for locomotion in Caenorhabditis elegans requires only the unc-49 gene. We cloned unc-49 and demonstrated that it possesses an unusual overlapping gene structure. unc-49 contains a single copy of a GABA receptor N terminus, followed by three tandem copies of a GABA receptor C terminus. Using a single promoter, unc-49 generates three distinct GABAA receptor-like subunits by splicing the N terminus to each of the three C-terminal repeats. This organization suggests that the three UNC-49 subunits (UNC-49A, UNC-49B, and UNC-49C) are coordinately rescued and therefore might coassemble to form a heteromultimeric GABA receptor. Surprisingly, only UNC-49B and UNC-49C are expressed at high levels, whereas UNC-49A expression is barely detectable. Green fluorescent protein-tagged UNC-49B and UNC-49C subunits are coexpressed in muscle cells and are colocalized to synaptic regions. UNC-49B and UNC-49C also coassemble efficiently in Xenopus oocytes and HEK-293 cells to form a heteromeric GABA receptor. Together these data argue that UNC-49B and UNC-49C coassemble at the C. elegans neuromuscular junction. Thus, C. elegans is able to encode a heteromeric GABA receptor with a single locus.
Bamber
B A
BA
Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
Beg
A A
AA
Twyman
R E
RE
Jorgensen
E M
EM
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D020043:Genes, Essential / Q000235:genetics; D017238:Genes, Helminth; D006801:Humans; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009469:Neuromuscular Junction / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D020033:Protein Isoforms / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D018079:Receptors, GABA / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013569:Synapses / Q000737:chemistry / Q000378:metabolism; D020080:Tandem Repeat Sequences / Q000235:genetics / Q000502:physiology; D014982:Xenopus laevis
D020033:Protein Isoforms; D012333:RNA, Messenger; D018079:Receptors, GABA