Genetic interactions among ADAMTS metalloproteases and basement membrane molecules in cell migration in Caenorhabditis elegans.

Genetic interactions among ADAMTS metalloproteases and basement membrane molecules in cell migration in Caenorhabditis elegans.
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秀丽隐杆线虫的细胞迁移中,ADAMTS金属蛋白酶和基底膜分子之间的遗传相互作用。

DOI:
10.1371/journal.pone.0240571
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发表时间:
2020
期刊:
影响因子:
3.7
通讯作者:
Nishiwaki K
Nishiwaki K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Imanishi A;Aoki Y;Kakehi M;Mori S;Takano T;Kubota Y;Kim HS;Shibata Y;Nishiwaki K

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在秀丽隐杆线虫性腺发育过程中,性腺前导细胞(称为远侧尖端细胞(DTC))以U形模式迁移形成U形性腺臂。ADAMTS(一种具有血小板反应蛋白基序的去整合素和金属蛋白酶)家族金属蛋白酶<$A-17和GON-1是正确的DTC迁移所必需的。mig-17的突变由于错误定向的DTC迁移而导致畸形的性腺,并且gon-1的突变由于DTC迁移的过早终止而导致缩短和肿胀的性腺。尽管mig-17和gon-1突变体显示的表型彼此非常不同,但在相同的基底膜蛋白基因中导致氨基酸取代的突变,emb-9/胶原IV α1,let-2/胶原IV α2和fbl-1/fibulin-1,被鉴定为mig-17和gon-1突变体的遗传抑制因子。为了理解这两种蛋白酶的共同作用,我们检测了mig-17抑制剂对gon-1的影响以及gon-1抑制剂和增强剂对mig-17性腺缺陷的影响。一些emb-9,let-2和fbl-1突变同时抑制mig-17和gon-1,而另一些只作用于mig-17或gon-1。这些结果表明,mig-17和gon-1在性腺形成方面既有其特定的功能,也有它们共同的功能。DTC基底膜中IV型胶原积累的水平在Gon-1突变体中显著高于野生型,并且当与抑制突变结合时降低至野生型水平,但不与增强突变结合,这表明降低IV型胶原水平的能力对于Gon-1抑制是重要的。
During development of the Caenorhabditis elegans gonad, the gonadal leader cells, called distal tip cells (DTCs), migrate in a U-shaped pattern to form the U-shaped gonad arms. The ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family metalloproteases MIG-17 and GON-1 are required for correct DTC migration. Mutations in mig-17 result in misshapen gonads due to the misdirected DTC migration, and mutations in gon-1 result in shortened and swollen gonads due to the premature termination of DTC migration. Although the phenotypes shown by mig-17 and gon-1 mutants are very different from one another, mutations that result in amino acid substitutions in the same basement membrane protein genes, emb-9/collagen IV α1, let-2/collagen IV α2 and fbl-1/fibulin-1, were identified as genetic suppressors of mig-17 and gon-1 mutants. To understand the roles shared by these two proteases, we examined the effects of the mig-17 suppressors on gon-1 and the effects of the gon-1 suppressors and enhancers on mig-17 gonadal defects. Some of the emb-9, let-2 and fbl-1 mutations suppressed both mig-17 and gon-1, whereas others acted only on mig-17 or gon-1. These results suggest that mig-17 and gon-1 have their specific functions as well as functions commonly shared between them for gonad formation. The levels of collagen IV accumulation in the DTC basement membrane were significantly higher in the gon-1 mutants as compared with wild type and were reduced to the wild-type levels when combined with suppressor mutations, but not with enhancer mutations, suggesting that the ability to reduce collagen IV levels is important for gon-1 suppression.
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