THE DROSOPHILA STUBBLE-STUBBLOID GENE ENCODES AN APPARENT TRANSMEMBRANE SERINE-PROTEASE REQUIRED FOR EPITHELIAL MORPHOGENESIS
THE DROSOPHILA STUBBLE-STUBBLOID GENE ENCODES AN APPARENT TRANSMEMBRANE SERINE-PROTEASE REQUIRED FOR EPITHELIAL MORPHOGENESIS
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DOI：
10.1073/pnas.90.11.4937
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发表时间：
1993-06-01
影响因子：
11.1
通讯作者：
FRISTROM, J
中科院分区：
文献类型：
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作者：
APPEL, LF;PROUT, M;FRISTROM, J
Sb-SBD基因是果蝇想象盘激素依赖性上皮形态发生所必需的，包括刚毛、腿和翅膀的形成。该基因是通过使用SB-SBD相关DNA损伤在263-kb基因组行走的20kb碱基(Kb)区域克隆的。该区域指定了一个几乎等于3.8kb的转录本，该转录本是由类固醇激素20-羟基蜕皮酮在体外培养的成像盘中诱导的。概念上翻译的蛋白是一个明显的786个残基的II型跨膜蛋白(N端入，C端出)，包括至少35个残基的胞内N末端结构域和244个残基的胞外C末端类胰蛋白酶样丝氨酸蛋白酶结构域。序列分析表明，SB-SBD编码的蛋白水解酶可以通过蛋白水解酶的切割来激活自身。与SB-SBD刷毛表型的细胞自主性一致，非催化N端片段和C端催化片段中的半胱氨酸残基之间的二硫键可以在激活后将蛋白酶拴在膜上。在刚毛形态发生过程中，显性SB突变和隐性SBD突变都会影响微丝束的组织。我们认为SB-SBD产品具有双重功能。(I)它通过其蛋白水解胞外域将想象中的椎间盘细胞从细胞外基质中分离出来，以及(Ii)它向其胞内域传递由外到内的信号，以改变细胞骨架，促进细胞形态发生的改变。
The Stubble-stubbloid (Sb-sbd) gene is required for hormone-dependent epithelial morphogenesis of imaginal discs of Drosophila, including the formation of bristles, legs, and wings. The gene has been cloned by using Sb-sbd-associated DNA lesions in a 20-kilobase (kb) region of a 263-kb genomic walk. The region specifies an almost-equal-to 3.8-kb transcript that is induced by the steroid hormone 20-hydroxyecdysone in imaginal discs cultured in vitro. The conceptually translated protein is an apparent 786-residue type II transmembrane protein (N terminus in, C terminus out), including an intracellular N-terminal domain of at least 35 residues and an extracellular C-terminal trypsin-like serine protease domain of 244 residues. Sequence analyses indicate that the Sb-sbd-encoded protease could activate itself by proteolytic cleavage. Consistent with the cell-autonomous nature of the Sb-sbd bristle phenotype, a disulfide bond between cysteine residues in the noncatalytic N-terminal fragment and the C-terminal catalytic fragment could tether the protease to the membrane after activation. Both dominant Sb and recessive sbd mutations affect the organization of microfilament bundles during bristle morphogenesis. We propose that the Sb-sbd product has a dual function. (i) It acts through its proteolytic extracellular domain to detach imaginal disc cells from extra-cellular matrices, and (ii) it transmits an outside-to-inside signal to its intracellular domain to modify the cytoskeleton and facilitate cell shape changes underlying morphogenesis.