Evidence for functional redundancy between C-elegans ADAM proteins SUP-17/Kuzbanian and ADM-4/TACE
Evidence for functional redundancy between C-elegans ADAM proteins SUP-17/Kuzbanian and ADM-4/TACE
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DOI：
10.1016/j.ydbio.2005.08.014
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发表时间：
2005-11-01
影响因子：
2.7
通讯作者：
Greenwald, I
中科院分区：
文献类型：
--
作者：
Jarriault, S;Greenwald, I
LIN-12/Notch蛋白的胞外蛋白酶在配体结合时被切割并脱落。在秀丽隐杆线虫中，遗传学证据表明果蝇Kuzbanian和哺乳动物ADAM 10的直系同源物<$-17是介导这一事件的蛋白酶。然而，在哺乳动物中，生化证据表明TACE是一种不同的ADAM蛋白。我们研究了sup-17和C. elegans TACE的直系同源物ADM-4，通过探索它们在lin-12/Notch基因介导的细胞命运决定中的作用。我们发现adm-4活性降低，就像sup-17活性降低一样，抑制了编码组成型活性受体的glp-1等位基因。此外，adm-4和sup-17活性的同时降低导致两性性腺中产生两个锚细胞，而不是lin-12活性丧失相关的一个a表型。两性体中sup-17和adm-4活性的同时降低导致高度渗透的合成不育。这似乎反映了受精囊的缺陷表达截短形式的LIN-12（减少胞外域脱落产物）可以挽救这种生育缺陷，这表明sup-17和adm-4可能介导LIN-12和/或GLP-1的胞外域脱落。我们的研究结果是一致的可能性，sup-17和adm-4是功能冗余的至少一个子集的LIN-12/Notch-介导的决定在C。优美的(c)2005年爱思唯尔公司All rights reserved.
The ectodoinain of LIN-12/Notch proteins is cleaved and shed upon ligand binding. In Caenorhabditis elegans, genetic evidence has implicated SUP-17, the ortholog of Drosophila Kuzbanian and mammalian ADAM10, as the protease that mediates this event. In mammals, however, biochemical evidence has implicated TACE, a different ADAM protein. We have investigated potential functional redundancy of sup-17 and the C. elegans ortholog of TACE, adm-4, by exploring their roles in cell fate decisions mediated by lin-12/Notch genes. We found that reduced adm-4 activity, like reduced sup-17 activity, suppresses an allele of glp-1 that encodes a constitutively active receptor. Furthermore, concomitant reduction of adm-4 and sup-17 activity causes the production of two anchor cells in the hermaphrodite gonad, instead of one-a phenotype associated with loss of lin-12 activity. Concomitant reduction of both sup-17 and adm-4 activity in hermaphrodites results in highly penetrant synthetic sterility. which appears to reflect a defect in the spermatheca. Expression of a truncated form of LIN-12 that minics the product of ectodomain shedding rescues this fertility defect, suggesting that sup-17 and adm-4 may mediate ectodomain shedding of LIN-12 and/or GLP-1. Our results are consistent with the possibility that sup-17 and adm-4 are functionally redundant for at least a subset of LIN-12/Notch-rnediated decisions in C. elegans. (c) 2005 Elsevier Inc. All rights reserved.