Sex-specific regulation of neuronal functions in Caenorhabditis elegans: the sex-determining protein TRA-1 represses goa-1/Gα(i/o)

Abstract

Females and males differ substantially in various neuronal functions in divergent, sexually dimorphic animal species, including humans. Despite its developmental, physiological and medical significance, understanding the molecular mechanisms by which sex-specific differences in the anatomy and operation of the nervous system are established remains a fundamental problem in biology. Here, we show that in Caenorhabditis elegans (nematodes), the global sex-determining factor TRA-1 regulates food leaving (mate searching), male mating and adaptation to odorants in a sex-specific manner by repressing the expression of goa-1 gene, which encodes the Gα (i/o) subunit of heterotrimeric G (guanine-nucleotide binding) proteins triggering physiological responses elicited by diverse neurotransmitters and sensory stimuli. Mutations in tra-1 and goa-1 decouple behavioural patterns from the number of X chromosomes. TRA-1 binds to a conserved binding site located in the goa-1 coding region, and downregulates goa-1 expression in hermaphrodites, particularly during embryogenesis when neuronal development largely occurs. These data suggest that the sex-determination machinery is an important modulator of heterotrimeric G protein-mediated signalling and thereby various neuronal functions in this organism and perhaps in other animal phyla.

Downregulation of transposable elements extends lifespan in Caenorhabditis elegans

“…Nematodes were maintained on standard Nematode Growth Medium (NGM) as described previously 69 , 70 , and fed with Escherichia coli OP50 bacteria. The following C. elegans strains were used in this study.…”

“…Nematodes were maintained on standard Nematode Growth Medium (NGM) as described previously 69,70 Prior to performing lifespan assays, VC2552 and VC40319 strains were isogenized by outcrossing 3 times with the wild type.…”

“…Lifespan assays were carried out at 15 °C, 20 °C and 25 °C, as described previously [69][70][71] . For synchronization, 20-30 gravid, well-fed adults were transferred to a new agar plate containing NGM seeded with E. coli [OP50 or HT115(DE3)] bacteria to lay embryos for 4-5 h, and then removed.…”

Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan

“…Three fem genes directly regulate the expression of tra-1 . Loss of function of fem-3 results in the hyperactivity of TRA-1 expression ( Szabó et al, 2009 ; Kutnyánszky et al, 2020 ) and promotes the development of hermaphrodites ( Starostina et al, 2007 ). TRA-1 is orthologous to the human GLI protein, a mediator of Sonic hedgehog signaling, which is involved in embryonic limb development ( Briscoe and Thérond, 2013 ), but also in tumorigenesis ( Coquenlorge et al, 2019 ), and was most recently identified as a suppressor of endometrial stem cell aging ( Cho et al, 2019 ).…”