- page settings
- showhide sidebar
- showhide empty fields
- layout
- (too narrow)
- open all
- close all
- Page Content
- Overview
- External Links
- History
- Referenced
- Tools
- Tree Display
- My WormBase
- My Favorites
- My Library
- Recent Activity
- Comments (0)
history logging is off
Tree Display
My Favorites
My Library
Comments on Pflugrad A et al. (1995) International C. elegans Meeting "UNC-37 ENCODES A GROUCHO-LIKE COFACTOR THAT MAY INTERACT WITH THE UNC-4 HOMEODOMAIN TO REGULATE NEURAL SPECIFICITY GENES" (0)
Overview
Pflugrad A, Barnes TM, & Miller DM (1995). UNC-37 ENCODES A GROUCHO-LIKE COFACTOR THAT MAY INTERACT WITH THE UNC-4 HOMEODOMAIN TO REGULATE NEURAL SPECIFICITY GENES presented in International C. elegans Meeting. Unpublished information; cite only with author permission.
Mutations in the UNC-4 homeodomain block reverse locomotion; VA motor neurons assume the pattern of synaptic input normally reserved for their sister cells, the VB motor neurons. Expression of a functional unc-4-lacZ reporter gene in the VAs restores normal movement to an unc-4 mutant. Thus, unc-4 is likely to regulate a differentiated feature of the VAs that allows presynaptic interneurons to distinguish them from VB sisters. In an effort to identify other genes that interact with unc-4, we screened for suppressors of a point mutation (e2322ts) in helix-2 of the unc-4 homeodomain. Four dominant, allele-specific suppressors of e2322ts are gain-of-function mutations in the unc-37 locus. We have cloned unc-37 by complementation of the hypomorphic allele unc-37(e262) which phenocopies the Unc-4 movement defect. unc- 37 encodes a 614 amino acid protein homologous to the highly conserved groucho-TLE (Drosophila-human) family of transcriptional cofactor proteins. The C-terminal region includes a tandem array of so-called WD-40 repeats which are thought to mediate specific protein-protein interactions. All four of the unc- 37 suppressors correspond to a single amino acid substitution (glu to lys) in one of the most highly conserved WD-40 domains (73% identity between human TLE and UNC-37). Strikingly, intragenic revertants of unc-4(e2322ts) are also glu to lys substitutions in helix-2 of the UNC-4 homeodomain. Our findings suggest a simple model: The helix-2 region of the UNC-4 homeodomain physically interacts with an UNC-37 WD-40 domain to regulate transcription of an unc-4 target gene. This idea is being tested using recombinant UNC-37 and UNC-4 proteins and by the yeast two-hybrid system.