Invadolysin: a novel, conserved metalloprotease links mitotic structural rearrangements with cell migration.
Invadolysin: a novel, conserved metalloprotease links mitotic structural rearrangements with cell migration.
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DOI：
10.1083/jcb.200405155
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发表时间：
2004-11-22
期刊：
影响因子：
--
通讯作者：
Heck MM
中科院分区：
文献类型：
--
作者：
McHugh B;Krause SA;Yu B;Deans AM;Heasman S;McLaughlin P;Heck MM
众所周知，细胞周期受磷酸化和泛素介导的蛋白水解网络的调节。在这里，我们描述了IX-14/侵入溶素，一种新的金属蛋白酶，只存在于后生动物，其活动似乎是必不可少的有丝分裂的进展。黑腹果蝇IX-14突变体幼虫的有丝分裂成神经细胞表现出核被膜蛋白水平增加，单极和不对称纺锤体，染色体长度出现超浓缩，周围有一圈松散浓缩的染色质。酶谱分析表明，蛋白酶活性，野生型幼虫的大脑中存在的，是从纯合组织失踪，我们表明，IX-14/侵入溶素裂解核纤层蛋白在体外。IX-14/侵袭溶素蛋白主要存在于类似于苍蝇和人类细胞中侵袭伪足的细胞质结构中，但显著地重新定位于迁移细胞的前缘。引人注目的是，我们发现，生殖细胞的定向迁移的影响，在果蝇IX-14突变胚胎。因此，侵入溶素确定了一个新的保守的金属蛋白酶家族，其活性似乎是协调有丝分裂进程所必需的，但也在细胞迁移中发挥了意想不到的作用。
The cell cycle is widely known to be regulated by networks of phosphorylation and ubiquitin-directed proteolysis. Here, we describe IX-14/invadolysin, a novel metalloprotease present only in metazoa, whose activity appears to be essential for mitotic progression. Mitotic neuroblasts of Drosophila melanogaster IX-14 mutant larvae exhibit increased levels of nuclear envelope proteins, monopolar and asymmetric spindles, and chromosomes that appear hypercondensed in length with a surrounding halo of loosely condensed chromatin. Zymography reveals that a protease activity, present in wild-type larval brains, is missing from homozygous tissue, and we show that IX-14/invadolysin cleaves lamin in vitro. The IX-14/invadolysin protein is predominantly found in cytoplasmic structures resembling invadopodia in fly and human cells, but is dramatically relocalized to the leading edge of migrating cells. Strikingly, we find that the directed migration of germ cells is affected in Drosophila IX-14 mutant embryos. Thus, invadolysin identifies a new family of conserved metalloproteases whose activity appears to be essential for the coordination of mitotic progression, but which also plays an unexpected role in cell migration.
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影响因子：
5.3
作者：
Krause, SA;Loupart, ML;Heck, MMS
通讯作者：
Heck, MMS
DOI：
10.1073/pnas.90.24.11473
发表时间：
1993-12-15
影响因子：
11.1
作者：
CONNELL, ND;MEDINAACOSTA, E;RUSSELL, DG
通讯作者：
RUSSELL, DG
DOI：
10.1073/pnas.110149597
发表时间：
2000-06-06
影响因子：
11.1
作者：
Clemens, JC;Worby, CA;Dixon, JE
通讯作者：
Dixon, JE
影响因子：
11.8
作者：
Levin, BR
通讯作者：
Levin, BR
影响因子：
9.2
作者：
Loupart, ML;Krause, SA;Heck, MMS
通讯作者：
Heck, MMS