Developmental Biology Research Initiative, Department of Biology, McGill University, Montréal, Québec, Canada.
PLoS One. 2010 Feb 4;5(2):e9048. doi: 10.1371/journal.pone.0009048.
Drosophila oogenesis is especially well suited for studying stem cell biology, cellular differentiation, and morphogenesis. The small modifier protein ubiquitin regulates many cellular pathways. Ubiquitin is conjugated to target proteins by a diverse class of enzymes called ubiquitin E3 ligases. Here we characterize the requirement of Cul-5, a key component of a subgroup of Cullin-RING-type ubiquitin E3 ligases, in Drosophila oogenesis. We find that reduced cul-5 activity causes the formation of aberrant follicles that are characterized by excess germ cells. We show that germ line cells overproliferate in cul-5 mutant females, causing the formation of abnormally large germ line cysts. Also, the follicular epithelium that normally encapsulates single germ line cysts develops aberrantly in cul-5 mutant, leading to defects in cyst formation. We additionally found that Cul-5 is required for germ cell maintenance, as germ cells are depleted in a substantial fraction of cul-5 mutant ovaries. All of these cul-5 phenotypes are strongly enhanced by reduced activity of gustavus (gus), which encodes a substrate receptor of Cul-5-based ubiquitin E3 ligases. Taken together, our results implicate Cul-5/Gus ubiquitin E3 ligases in ovarian tissue morphogenesis, germ cell proliferation and maintenance of the ovarian germ cell population.
果蝇卵子发生特别适合研究干细胞生物学、细胞分化和形态发生。小修饰蛋白泛素调节许多细胞途径。泛素通过称为泛素 E3 连接酶的多种酶类连接到靶蛋白上。在这里，我们描述了 Cul-5（Cullin-RING 型泛素 E3 连接酶亚群的关键组成部分）在果蝇卵子发生中的必需性。我们发现降低 cul-5 活性会导致形成异常的滤泡，其特征是过多的生殖细胞。我们表明，生殖系细胞在 cul-5 突变体雌性中过度增殖，导致异常大的生殖系胞囊形成。此外，通常包裹单个生殖系胞囊的滤泡上皮在 cul-5 突变体中异常发育，导致胞囊形成缺陷。我们还发现 Cul-5 对于生殖细胞的维持是必需的，因为在大量 cul-5 突变体卵巢中生殖细胞耗尽。所有这些 cul-5 表型都被 gustavus（gus）的活性降低强烈增强，gus 编码 Cul-5 基泛素 E3 连接酶的底物受体。总之，我们的结果表明 Cul-5/Gus 泛素 E3 连接酶参与卵巢组织形态发生、生殖细胞增殖和卵巢生殖细胞群体的维持。
