Negative regulation of male development in Caenorhabditis elegans by a protein-protein interaction between TRA-2A and FEM-3
Negative regulation of male development in Caenorhabditis elegans by a protein-protein interaction between TRA-2A and FEM-3
复制标题
DOI：
10.1101/gad.13.11.1453
复制
发表时间：
1999-06-01
影响因子：
10.5
通讯作者：
Spence, AM
中科院分区：
文献类型：
--
作者：
Mehra, A;Gaudet, J;Spence, AM
线虫秀丽线虫的tra-2基因编码一种膜蛋白TRA-2A，可促进XX雌雄同体的发育。遗传分析表明，tra-2是男性发育所必需的三个基因的负调控基因：fem-L、fem-2和fem-3。我们报道了在酵母双杂交系统和体外实验中，TRA-2A的羧基末端区域与FE-3发生了特异性的相互作用。我们发现，过量的Fem-3可以克服tra-2的雌性化效应，并导致XX个体细胞组织的广泛雄性化，这一观点与fem-3是负调控的靶点一致。反过来，我们证明了过量的FE-3的雄性化效应可以被TRA-2A的羧基末端结构域的过量生产所抑制。保持TRA-2A结合活性的fem-3片段可以雄性化fem-3(+)动物，但不能使fem-3突变体雄性化，这表明有可能通过滴定TRA-2A来释放和激活内源性fem-3。我们认为，TRA-2A通过直接与FEM-3相互作用来阻止男性发育，TRA-2A和FE-3相反活动之间的平衡决定了体细胞组织中性别特异的细胞命运。当平衡有利于FEM3时，它通过或与其他FEM蛋白一起作用，促进雄性细胞的命运。
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-l, 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.