Tetraspanin CD63 promotes targeting and lysosomal proteolysis of membrane-type 1 matrix metalloproteinase

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is known to be internalized from cell surface, however, the fate of internalized MT1-MMP is still unknown. Here we demonstrate that at least a part of internalized MT1-MMP is targeted for lysosomal proteolysis. Treatment with an inhibitor of lysosom...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2003-04, Vol.304 (1), p.160-166
Main Authors: Takino, Takahisa, Miyamori, Hisashi, Kawaguchi, Noriko, Uekita, Takamasa, Seiki, Motoharu, Sato, Hiroshi
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - analysis
Antigens, CD - chemistry
Antigens, CD - physiology
CD63
Cell Line
Dogs
Down-Regulation
HeLa Cells
Humans
Internalization
Lysosomes
Lysosomes - chemistry
Lysosomes - metabolism
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases - analysis
Metalloendopeptidases - chemistry
Metalloendopeptidases - metabolism
Microscopy, Confocal
MMP
MT1-MMP
Platelet Membrane Glycoproteins - analysis
Platelet Membrane Glycoproteins - chemistry
Platelet Membrane Glycoproteins - physiology
Protein Transport
Proteolysis
Sequence Deletion
Tetraspanin 30
Tetraspanins
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Summary:Membrane-type 1 matrix metalloproteinase (MT1-MMP) is known to be internalized from cell surface, however, the fate of internalized MT1-MMP is still unknown. Here we demonstrate that at least a part of internalized MT1-MMP is targeted for lysosomal proteolysis. Treatment with an inhibitor of lysosomal proteinases chloroquine suppressed degradation of internalized MT1-MMP and induced accumulation of MT1-MMP in CD63-positive lysosomes. Ectopic expression of CD63 accelerated degradation of MT1-MMP, which was blocked by chloroquine. MT1-MMP, and CD63 were shown to form a complex through hemopexin-like domain of MT1-MMP and N-terminal region of CD63, and thus accelerated degradation of MT1-MMP was not observed with mutants lacking these domains. CD63 mutant lacking lysosomal targeting motif was unable to promote MT1-MMP degradation. These results suggest that CD63 regulates MT1-MMP by targeting to lysosomes.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(03)00544-8