RRC ID 65307
Author Bayer EA, Stecky RC, Neal L, Katsamba PS, Ahlsen G, Balaji V, Hoppe T, Shapiro L, Oren-Suissa M, Hobert O.
Title Ubiquitin-dependent regulation of a conserved DMRT protein controls sexually dimorphic synaptic connectivity and behavior.
Journal Elife
Abstract 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.
Volume 9
Published 2020-10-6
DOI 10.7554/eLife.59614
PII 59614
PMID 33021200
PMC PMC7538159
MeSH Animals Behavior, Animal Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Disorders of Sex Development Female Gene Knockout Techniques Humans Male Neurons / metabolism* Sex Characteristics* Synaptic Transmission / genetics Transcription Factors* / genetics Transcription Factors* / metabolism Ubiquitin / metabolism*
Resource
C.elegans tm1951