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Ubiquitin-dependent regulation of a conserved DMRT protein controls sexually dimorphic synaptic connectivity and behavior.

Emily A Bayer | Rebecca C Stecky | Lauren Neal | Phinikoula S Katsamba | Goran Ahlsen | Vishnu Balaji | Thorsten Hoppe | Lawrence Shapiro | Meital Oren-Suissa | Oliver Hobert
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.

Pubmed ID: 33021200

Research resources used in this publication

None found

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Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NINDS NIH HHS, United States
    Id: F31 NS096863
  • Agency: NIH HHS, United States
    Id: R37 NS039996
  • Agency: NINDS NIH HHS, United States
    Id: R37 NS039996

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