Ubiquitin-dependent regulation of a conserved DMRT protein controls sexually dimorphic synaptic connectivity and behavior.
Emily A BayerRebecca C SteckyLauren NealPhinikoula S KatsambaGoran AhlsenVishnu BalajiThorsten HoppeLawrence ShapiroMeital Oren-SuissaOliver HobertPublished in: eLife (2020)
Sex-specific synaptic connectivity is beginning to emerge as a remarkable, but little explored feature of animal brains. We describe here a novel mechanism that promotes sexually dimorphic neuronal function and synaptic connectivity in the nervous system of the nematode Caenorhabditis elegans. We demonstrate that a phylogenetically conserved, but previously uncharacterized Doublesex/Mab-3 related transcription factor (DMRT), dmd-4, is expressed in two classes of sex-shared phasmid neurons specifically in hermaphrodites but not in males. We find dmd-4 to promote hermaphrodite-specific synaptic connectivity and neuronal function of phasmid sensory neurons. Sex-specificity of DMD-4 function is conferred by a novel mode of posttranslational regulation that involves sex-specific protein stabilization through ubiquitin binding to a phylogenetically conserved but previously unstudied protein domain, the DMA domain. A human DMRT homolog of DMD-4 is controlled in a similar manner, indicating that our findings may have implications for the control of sexual differentiation in other animals as well.
Keyphrases
- transcription factor
- duchenne muscular dystrophy
- resting state
- functional connectivity
- white matter
- muscular dystrophy
- protein protein
- prefrontal cortex
- small molecule
- spinal cord
- endothelial cells
- amino acid
- binding protein
- mental health
- spinal cord injury
- cerebral ischemia
- blood brain barrier
- brain injury
- structural basis
- drug induced