Regulation of MT1-MMP Activity through Its Association with ERMs
| Autor: | Víctor Toribio, Moreno Zamai, Laura Genís, Henar Suárez, María Victoria Hernández-Riquer, Soraya López-Martín, María Yáñez-Mó, Alicia G. Arroyo |
|---|---|
| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Fundación Ramón Areces, UAM. Departamento de Biología Molecular, Instituto de Salud Carlos III, Fundación ProCNIC, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Fundación Pro CNIC |
| Rok vydání: | 2019 |
| Předmět: |
media_common.quotation_subject
Moesin Tetraspanin enriched-microdomains macromolecular substances Tetraspanin 24 Article Ezrin Membrane Microdomains tetraspanin enriched-microdomains Tetraspanin stomatognathic system Protein Domains Radixin MT1-MMP Matrix Metalloproteinase 14 Humans Secretion Amino Acid Sequence Cytoskeleton Internalization lcsh:QH301-705.5 media_common Binding Sites Chemistry Microfilament Proteins Membrane Proteins General Medicine Extracellular vesicles Biología y Biomedicina / Biología Cell biology Cytoskeletal Proteins lcsh:Biology (General) ERM Invadopodia embryonic structures Mutation MCF-7 Cells extracellular vesicles Protein Binding Subcellular Fractions |
| Zdroj: | Cells Biblos-e Archivo: Repositorio Institucional de la UAM Universidad Autónoma de Madrid Cells, Vol 9, Iss 2, p 348 (2020) Repisalud Instituto de Salud Carlos III (ISCIII) Volume 9 Issue 2 Digital.CSIC. Repositorio Institucional del CSIC instname Digital.CSIC: Repositorio Institucional del CSIC Consejo Superior de Investigaciones Científicas (CSIC) Biblos-e Archivo. Repositorio Institucional de la UAM |
| ISSN: | 2073-4409 |
| Popis: | © 2020 by the authors. Membrane-bound proteases play a key role in biology by degrading matrix proteins or shedding adhesion receptors. MT1-MMP metalloproteinase is critical during cancer invasion, angiogenesis, and development. MT1-MMP activity is strictly regulated by internalization, recycling, autoprocessing but also through its incorporation into tetraspanin-enriched microdomains (TEMs), into invadopodia, or by its secretion on extracellular vesicles (EVs). We identified a juxtamembrane positively charged cluster responsible for the interaction of MT1-MMP with ERM (ezrin/radixin/moesin) cytoskeletal connectors in breast carcinoma cells. Linkage to ERMs regulates MT1-MMP subcellular distribution and internalization, but not its incorporation into extracellular vesicles. MT1-MMP association to ERMs and insertion into TEMs are independent phenomena, so that mutation of the ERM-binding motif in the cytoplasmic region of MT1-MMP does not preclude its association with the tetraspanin CD151, but impairs the accumulation and coalescence of CD151/MT1-MMP complexes at actin-rich structures. Conversely, gene deletion of CD151 does not impact on MT1-MMP colocalization with ERM molecules. At the plasma membrane MT1-MMP autoprocessing is severely dependent on ERM association and seems to be the dominant regulator of the enzyme collagenolytic activity. This newly characterized MT1-MMP/ERM association can thus be of relevance for tumor cell invasion. This work has been supported by grants BFU2014-55478-R, REDIEX. SAF2015-71231-REDT and BIO2017-86500-R from Ministerio Español de Economía y Competitividad (MINECO) and by a grant from Fundación Ramón Areces “Ayudas a la Investigación en Ciencias de la Vida y de la Materia, 2014” to M.Y.-M. H.S. was supported by a FPI-UAM fellowship. The CNIC is supported by the Ministry of Ciencia, Innovacion y Universidades and the Pro CNIC Foundation, is a Severo Ochoa Center of Excellence (SEV-2015-0505), also supported by European Regional Development Fund (FEDER) “Una manera de hacer Europa”. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|