Cellular and Molecular Life Sciences

, Volume 68, Issue 20, pp 3323–3335

Functional interplay between tetraspanins and proteases

Review

DOI: 10.1007/s00018-011-0746-y

Cite this article as:
Yáñez-Mó, M., Gutiérrez-López, M.D. & Cabañas, C. Cell. Mol. Life Sci. (2011) 68: 3323. doi:10.1007/s00018-011-0746-y

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.

Keywords

TetraspaninsMMPADAMSα-secretasesSheddingRIP

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

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Servicio de Inmunología, Hospital de la PrincesaInstituto de Investigación Sanitaria PrincesaMadridSpain
  2. 2.Facultad de Medicina, Departamento de FarmacologíaUCMMadridSpain
  3. 3.Centro de Biología Molecular Severo Ochoa (CSIC-UAM)MadridSpain
  4. 4.Facultad de Medicina, Departamento de Microbiología I (Inmunología)UCMMadridSpain