Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Movement / physiology*
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Cell Nucleus / genetics
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Cell Nucleus / metabolism*
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Cells, Cultured
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Chromosome Aberrations / embryology
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Conserved Sequence / genetics
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Cytoplasm / metabolism
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Drosophila Proteins / genetics
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Drosophila Proteins / isolation & purification
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Drosophila Proteins / metabolism*
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Drosophila melanogaster
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Germ Cells / cytology
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Germ Cells / metabolism
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HeLa Cells
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Humans
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Lamin Type A / metabolism
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Larva / cytology
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Larva / growth & development
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Larva / metabolism
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Macrophages
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Metalloendopeptidases / genetics
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Metalloendopeptidases / isolation & purification
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Metalloendopeptidases / metabolism*
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Metalloproteases / genetics
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Metalloproteases / isolation & purification
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Metalloproteases / metabolism*
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Mitosis / physiology*
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Models, Molecular
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Molecular Sequence Data
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Mutation / genetics
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Nuclear Envelope / metabolism
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
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Spindle Apparatus / genetics
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Spindle Apparatus / metabolism
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Stem Cells / cytology
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Stem Cells / metabolism
Substances
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DNA, Complementary
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Drosophila Proteins
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Lamin Type A
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Metalloproteases
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Metalloendopeptidases
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invadolysin, Drosophila
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invadolysin, human