Dimerization activates the Inversin complex in C. elegans
Biorxiv : the Preprint Server for Biology
|May 27, 2024
Summary
The Inversin complex, crucial for tissue patterning, is activated by dimerization. Monomerization suppresses its activity, revealing dynamic states that control organ physiology.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Ankyrin repeat-containing proteins Inversin (INVS) and ANKS6, along with NEK8 kinase, are implicated in tissue patterning and organ physiology.
- The dynamic assembly and functional states of the Inversin complex remain poorly understood.
Approach:
- Utilized hyperactive alleles in *C. elegans* to investigate the Inversin complex's activation mechanism.
- Employed genome engineering to tag nematode homologs of INVS (MLT-4) and NEK8 (NEKL-2) with RFP.
- Applied optogenetics to stimulate and inhibit dimerization of MLT-4 and NEKL-2.
Key Points:
- Dimerization of the Inversin complex activates its function, leading to gain-of-function phenotypes.
- Monomerization of fluorescent tags suppressed the observed hyperactive phenotype.
- Optogenetically induced dimerization mimicked a constitutively active Inversin complex.
- Dimerization of NEKL-2 rescued a lethal MLT-4 mutant, highlighting the functional requirement of the dimeric state.
Conclusions:
- The Inversin complex exists in at least two distinct functional states: an active dimer and an inactive monomer.
- Dynamic switching between these states regulates the output of the Inversin complex, controlling tissue patterning and organ physiology.
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