Regulation of MT1-MMP Activity through Its Association with ERMs
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/2/348 |
| _version_ | 1797708219459567616 |
|---|---|
| author | Henar Suárez Soraya López-Martín Víctor Toribio Moreno Zamai M. Victoria Hernández-Riquer Laura Genís Alicia G. Arroyo María Yáñez-Mó |
| author_facet | Henar Suárez Soraya López-Martín Víctor Toribio Moreno Zamai M. Victoria Hernández-Riquer Laura Genís Alicia G. Arroyo María Yáñez-Mó |
| author_sort | Henar Suárez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T06:18:07Z |
| format | Article |
| id | doaj.art-d627c74cda27402f9b2d9476c204dcb5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:18:07Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d627c74cda27402f9b2d9476c204dcb52023-09-03T02:24:52ZengMDPI AGCells2073-44092020-02-019234810.3390/cells9020348cells9020348Regulation of MT1-MMP Activity through Its Association with ERMsHenar Suárez0Soraya López-Martín1Víctor Toribio2Moreno Zamai3M. Victoria Hernández-Riquer4Laura Genís5Alicia G. Arroyo6María Yáñez-Mó7Molecular Biology Department, Universidad Autónoma de Madrid (UAM), 28049 Madrid, SpainSevero Ochoa Molecular Biology Center (CBM-SO), Instituto de Investigación Sanitaria Princesa (IIS-IP), 28049 Madrid, SpainMolecular Biology Department, Universidad Autónoma de Madrid (UAM), 28049 Madrid, SpainUnit of Microscopy and Dynamic Imaging, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, SpainVascular Pathophysiology Department, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, SpainVascular Pathophysiology Department, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, SpainVascular Pathophysiology Department, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, SpainMolecular Biology Department, Universidad Autónoma de Madrid (UAM), 28049 Madrid, SpainMembrane-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.https://www.mdpi.com/2073-4409/9/2/348mt1-mmpermtetraspanin enriched-microdomainsextracellular vesicles |
| spellingShingle | Henar Suárez Soraya López-Martín Víctor Toribio Moreno Zamai M. Victoria Hernández-Riquer Laura Genís Alicia G. Arroyo María Yáñez-Mó Regulation of MT1-MMP Activity through Its Association with ERMs Cells mt1-mmp erm tetraspanin enriched-microdomains extracellular vesicles |
| title | Regulation of MT1-MMP Activity through Its Association with ERMs |
| title_full | Regulation of MT1-MMP Activity through Its Association with ERMs |
| title_fullStr | Regulation of MT1-MMP Activity through Its Association with ERMs |
| title_full_unstemmed | Regulation of MT1-MMP Activity through Its Association with ERMs |
| title_short | Regulation of MT1-MMP Activity through Its Association with ERMs |
| title_sort | regulation of mt1 mmp activity through its association with erms |
| topic | mt1-mmp erm tetraspanin enriched-microdomains extracellular vesicles |
| url | https://www.mdpi.com/2073-4409/9/2/348 |
| work_keys_str_mv | AT henarsuarez regulationofmt1mmpactivitythroughitsassociationwitherms AT sorayalopezmartin regulationofmt1mmpactivitythroughitsassociationwitherms AT victortoribio regulationofmt1mmpactivitythroughitsassociationwitherms AT morenozamai regulationofmt1mmpactivitythroughitsassociationwitherms AT mvictoriahernandezriquer regulationofmt1mmpactivitythroughitsassociationwitherms AT lauragenis regulationofmt1mmpactivitythroughitsassociationwitherms AT aliciagarroyo regulationofmt1mmpactivitythroughitsassociationwitherms AT mariayanezmo regulationofmt1mmpactivitythroughitsassociationwitherms |