Dimerization activates the Inversin complex in C. elegans
Erika Beyrent1,2, Derek T Wei1,2, Gwendolyn M Beacham1,2
1Department of Molecular Medicine, Cornell University, Ithaca, NY 14853.
Molecular Biology of the Cell
|August 7, 2024
Summary
The Inversin complex, crucial for tissue patterning, is activated by dimerization. This study reveals that dynamic switching between monomer and dimer states controls the complex's function.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- Ankyrin repeat-containing proteins Inversin (INVS) and ANKS6, along with NEK8 kinase, are implicated in tissue patterning and organ physiology.
- The precise assembly and functional states of the Inversin complex remain unclear.
Purpose of the Study:
- To investigate the functional states of the Inversin complex.
- To determine if dimerization regulates the activity of the Inversin complex.
Main Methods:
- Characterization of hyperactive alleles in *C. elegans*.
- Genome engineering to tag nematode homologs of INVS (MLT-4) and NEK8 (NEKL-2).
- Optogenetic stimulation to induce or suppress dimerization.
Main Results:
- Dimerization was discovered to activate the Inversin complex.
- RFP-tagged MLT-4 and NEKL-2 induced a cyst-like phenotype, suppressed by monomerization.
- Optogenetically induced dimerization recapitulated constitutive activation, and NEKL-2 dimerization bypassed a lethal MLT-4 mutant.
Conclusions:
- The Inversin complex exists in at least two states: an active dimer and an inactive monomer.
- Dynamic switching between these states regulates the complex's output, essential for organ physiology and tissue patterning.
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