Functional interplay between tetraspanins and proteases

Several recent publications have described examples of physical and functional interations between tetraspanins and specific membrane proteases belonging to the TM-MMP and α-(ADAMs) and γ-secretases families. Collectively, these examples constitute an emerging body of evidence supporting the notion...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2011-10, Vol.68 (20), p.3323-3335
Main Authors: Yáñez-Mó, María, Gutiérrez-López, Maria Dolores, Cabañas, Carlos
Format: Article
Language:English
Subjects:
ADAM Proteins - metabolism
Alzheimer's disease
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cellular biology
Enzymes
Humans
Life Sciences
Matrix Metalloproteinases - metabolism
Membrane Proteins - metabolism
Membranes
Peptide Hydrolases - metabolism
Peptides
Proteases
Review
Signal transduction
Tetraspanins
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Summary:Several recent publications have described examples of physical and functional interations between tetraspanins and specific membrane proteases belonging to the TM-MMP and α-(ADAMs) and γ-secretases families. Collectively, these examples constitute an emerging body of evidence supporting the notion that tetraspanin-enriched microdomains (TEMs) represent functional platforms for the regulation of key cellular processes including the release of surface protein ectodomains ("shedding"), regulated intramembrane proteolysis ("RIPing") and matrix degradation and assembly. These cellular processes in turn play a crucial role in an array of physiological and pathological phenomena. Thus, TEMs may represent new therapeutical targets that may simultaneously affect the proteolytic activity of different enzymes and their substrates. Agonistic or antagonistic antibodies and blocking soluble peptides corresponding to tetraspanin functional regions may offer new opportunities in the treatment of pathologies such as chronic inflammation, cancer, or Alzheimer's disease. In this review article, we will discuss all these aspects of functional regulation of protease activities by tetraspanins.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-011-0746-y