Negative regulation of male development in Caenorhabditis elegans by a protein-protein interaction between TRA-2A and FEM-3.
The tra-2 gene of the nematode Caenorhabditis elegans encodes a predicted membrane protein, TRA-2A, that promotes XX hermaphrodite development. Genetic analysis suggests that tra-2 is a negative regulator of three genes that are required for male development: fem-1, fem-2, and fem-3. We report that the carboxy-terminal region of TRA-2A interacts specifically with FEM-3 in the yeast two-hybrid system and in vitro. Consistent with the idea that FEM-3 is a target of negative regulation, we find that excess FEM-3 can overcome the feminizing effect of tra-2 and cause widespread masculinization of XX somatic tissues. In turn, we show that the masculinizing effects of excess FEM-3 can be suppressed by overproduction of the carboxy-terminal domain of TRA-2A. A FEM-3 fragment that retains TRA-2A-binding activity can masculinize fem-3(+) animals, but not fem-3 mutants, suggesting that it is possible to release and to activate endogenous FEM-3 by titrating TRA-2A. We propose that TRA-2A prevents male development by interacting directly with FEM-3 and that a balance between the opposing activities of TRA-2A and FEM-3 determines sex-specific cell fates in somatic tissues. When the balance favors FEM-3, it acts through or with the other FEM proteins to promote male cell fates.
Mehra
A
A
Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada, M5S 1A8.
Gaudet
J
J
Heck
L
L
Kuwabara
P E
PE
Spence
A M
AM
D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D005260:Female; D018869:Heat-Shock Response; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases; D012441:Saccharomyces cerevisiae; D012733:Sex Differentiation / Q000235:genetics*; D019076:Transgenes
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C115306:FEM-1 protein, C elegans; D015801:Helminth Proteins; D008565:Membrane Proteins; C075059:fem-3 protein, C elegans; C076107:tra-2 protein, C elegans; C097435:Fem-2 protein, C elegans; D010749:Phosphoprotein Phosphatases