C. elegans ADAMTS ADT-2 regulates body size by modulating TGFβ signaling and cuticle collagen organization.
C. elegans ADAMTS ADT-2 regulates body size by modulating TGFβ signaling and cuticle collagen organization.
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DOI：
10.1016/j.ydbio.2011.01.016
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发表时间：
2011-04-01
影响因子：
2.7
通讯作者：
Savage-Dunn C
中科院分区：
文献类型：
--
作者：
Fernando T;Flibotte S;Xiong S;Yin J;Yzeiraj E;Moerman DG;Meléndez A;Savage-Dunn C
机体生长和体型大小受遗传和环境因素的影响。我们已经利用强大的分子遗传技术，在线虫秀丽隐杆线虫鉴定体型的遗传决定因素。在秀丽隐杆线虫中，DBL-1是被称为转化生长因子β超家族的保守分泌生长因子家族的成员，已知在生长控制中起主要作用。然而，身体大小的其他决定因素发挥作用的机制却不太清楚。为了确定参与体型调节的其他基因，先前进行了小突变体的遗传筛选。在筛选中发现的基因之一是sma-21。我们现在证明sma-21编码ADT-2， ADT-2是分泌的金属蛋白酶ADAMTS（一种具有血栓反应蛋白基元的崩解素和金属蛋白酶）家族的成员。ADAMTS蛋白被认为可以重塑细胞外基质，并可能调节细胞外信号的活性。遗传相互作用表明ADT-2与多种大小调节途径并行或在多种途径中起作用。我们证明ADT-2是正常水平表达dbl -1应答转录报告基因所必需的。我们进一步证明adt-2调控序列驱动胶质样细胞和外阴细胞的表达，并且adt-2活性是正常角质层胶原纤维组织所必需的。因此，我们提出ADT-2通过调节tgf - β信号活性和维持正常角质层结构来调节体型。
Organismal growth and body size are influenced by both genetic and environmental factors. We have utilized the strong molecular genetic techniques available in the nematode C. elegans to identify genetic determinants of body size. In C. elegans, DBL-1, a member of the conserved family of secreted growth factors known as the Transforming Growth Factor β superfamily, is known to play a major role in growth control. The mechanisms by which other determinants of body size function, however, is less well understood. To identify additional genes involved in body size regulation, a genetic screen for small mutants was previously performed. One of the genes identified in that screen was sma-21. We now demonstrate that sma-21 encodes ADT-2, a member of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted metalloproteases. ADAMTS proteins are believed to remodel the extracellular matrix and may modulate the activity of extracellular signals. Genetic interactions suggest that ADT-2 acts in parallel with or in multiple size regulatory pathways. We demonstrate that ADT-2 is required for normal levels of expression of a DBL-1-responsive transcriptional reporter. We further demonstrate that adt-2 regulatory sequences drive expression in glial-like and vulval cells, and that ADT-2 activity is required for normal cuticle collagen fibril organization. We therefore propose that ADT-2 regulates body size both by modulating TGFβ signaling activity and by maintaining normal cuticle structure.
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影响因子：
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通讯作者：
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