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Functional interplay between tetraspanins and proteases

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Abstract

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.

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Abbreviations

AD:

Alzheimer's disease

ADAM:

A disintegrin and metalloprotease domain

APP:

Amyloid precursor protein

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

GPCRs:

G protein-coupled receptors

HB-EGF:

Heparin-binding epidermal growth factor

ICAM-1:

Intercellular adhesion molecule-1

mAbs:

Monoclonal antibodies

MT1-MMP:

Membrane-type-1-matrix metalloprotease

PMA:

Phorbol-12-myristate-13-acetate

RIP:

Regulated intramembrane proteolysis

TEMs:

Tetraspanin-enriched microdomains

TMPS:

Triple membrane-passing signaling

TNFα:

Tumor necrosis factor-α

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Acknowledgments

This work was supported by grants BFU2007-66443/BMC and BFU2010-19144/BMC from Ministerio de Ciencia e Innovación, a grant from Fundación de Investigación Médica Mutua Madrileña and by the RETICS Program RD08/0075-RIER (Red de Inflamación y Enfermedades Reumáticas) from Instituto de Salud Carlos III (to C.C.), a grant from Fundación de Investigación Médica Mutua Madrileña (to M.D.G.L.), and the grant PI080794 from Instituto de Salud Carlos III (to M.Y-M).

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Authors and Affiliations

  1. Servicio de Inmunología, Hospital de la Princesa, Instituto de Investigación Sanitaria Princesa, 28006, Madrid, Spain

    María Yáñez-Mó

  2. Facultad de Medicina, Departamento de Farmacología, UCM, 28040, Madrid, Spain

    Maria Dolores Gutiérrez-López

  3. Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049, Madrid, Spain

    Carlos Cabañas

  4. Facultad de Medicina, Departamento de Microbiología I (Inmunología), UCM, 28040, Madrid, Spain

    Carlos Cabañas

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  1. María Yáñez-Mó
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  2. Maria Dolores Gutiérrez-López
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  3. Carlos Cabañas
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Correspondence to María Yáñez-Mó, Maria Dolores Gutiérrez-López or Carlos Cabañas.

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Yáñez-Mó, M., Gutiérrez-López, M.D. & Cabañas, C. Functional interplay between tetraspanins and proteases. Cell. Mol. Life Sci. 68, 3323–3335 (2011). https://doi.org/10.1007/s00018-011-0746-y

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  • DOI: https://doi.org/10.1007/s00018-011-0746-y

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