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Dimerization activates the Inversin complex in C. elegans
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DOI：10.1091/mbc.E24-05-0218.png)
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Abstract
En 中文
Genetic, colocalization, and biochemical studies suggest that the ankyrin repeat-containing proteins Inversin (INVS) and ANKS6 function with the NEK8 kinase to control tissue patterning and maintain organ physiology. It is unknown whether these three proteins assemble into a static Inversin complex or one that adopts multiple bioactive forms. Through the characterization of hyperactive alleles in C. elegans, , we discovered that the Inversin complex is activated by dimerization. Genome engineering of an RFP tag onto the nematode homologues of INVS (MLT-4) and NEK8 (NEKL-2) induced a gain-of-function, cyst-like phenotype that was suppressed by monomerization of the fluorescent tag. Stimulated dimerization of MLT-4 or NEKL-2 using optogenetics was sufficient to recapitulate the phenotype of a constitutively active Inversin complex. Further, dimerization of NEKL2 bypassed a lethal MLT-4 mutant, demonstrating that the dimeric form is required for function. We propose that dynamic switching between at least two functionally distinct states - an active dimer and an inactive monomer - gates the output of the Inversin complex.
Keywords:
RED FLUORESCENT PROTEIN
NEK8 MUTATIONS
NEPHRONOPHTHISIS
INV
GENE
ADAPTATION
ASYMMETRY
REVEALS
KINASES
CILIARY
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