Negative regulation of male development in Caenorhabditis elegans by a protein–protein interaction between TRA-2A and FEM-3 (original) (raw)
- Arun Mehra,
- Jeb Gaudet,
- Linda Heck,
- Patricia E. Kuwabara, and
- Andrew M. Spence
- Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada, M5S 1A8; Medical Research Council (MRC), Laboratory of Molecular Biology, Cambridge CB2 2QH UK
Abstract
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.
