A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44
| Autor: | Svenja Riedle, Andreas Ludwig, Peter Altevogt, François Le Naour, Steffen Runz, Paul Gutwein, Michael P. Sanderson, Sascha Keller, Eric Rubinstein, Alexander Stoeck |
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| Rok vydání: | 2005 |
| Předmět: |
Endosome
Neural Cell Adhesion Molecule L1 Biology ADAM17 Protein Cleavage (embryo) Biochemistry Exosome Exocytosis chemistry.chemical_compound ADAM10 Protein Cell Line Tumor Humans Molecular Biology Cellular compartment Cytoplasmic Vesicles Membrane Proteins Cell Biology Cell biology Protein Structure Tertiary ADAM Proteins Hyaluronan Receptors chemistry Ectodomain Gene Expression Regulation Ionomycin RNA Interference Amyloid Precursor Protein Secretases Research Article |
| Zdroj: | The Biochemical journal. 393(Pt 3) |
| ISSN: | 1470-8728 |
| Popis: | Ectodomain shedding is a proteolytic mechanism by which transmembrane molecules are converted into a soluble form. Cleavage is mediated by metalloproteases and proceeds in a constitutive or inducible fashion. Although believed to be a cell-surface event, there is increasing evidence that cleavage can take place in intracellular compartments. However, it is unknown how cleaved soluble molecules get access to the extracellular space. By analysing L1 (CD171) and CD44 in ovarian carcinoma cells, we show in the present paper that the cleavage induced by ionomycin, APMA (4-aminophenylmercuric acetate) or MCD (methyl-β-cyclodextrin) is initiated in an endosomal compartment that is subsequently released in the form of exosomes. Calcium influx augmented the release of exosomes containing functionally active forms of ADAM10 (a disintegrin and metalloprotease 10) and ADAM17 [TACE (tumour necrosis factor α-converting enzyme)] as well as CD44 and L1 cytoplasmic cleavage fragments. Cleavage could also proceed in released exosomes, but only depletion of ADAM10 by small interfering RNA blocked cleavage under constitutive and induced conditions. In contrast, cleavage of L1 in response to PMA occurred at the cell surface and was mediated by ADAM17. We conclude that different ADAMs are involved in distinct cellular compartments and that ADAM10 is responsible for shedding in vesicles. Our findings open up the possibility that exosomes serve as a platform for ectodomain shedding and as a vehicle for the cellular export of soluble molecules. |
| Databáze: | OpenAIRE |
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