Regulation of Leukocytes by TspanC8 Tetraspanins and the “Molecular Scissor” ADAM10
A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane protein that functions as a “molecular scissor” to cleave the extracellular regions from its transmembrane target proteins. ADAM10 is well characterized as the ligand-dependent activator of Notch proteins, which control ce...
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| Format: | Article |
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01451/full |
| _version_ | 1818619865955565568 |
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| author | Alexandra L. Matthews Chek Ziu Koo Chek Ziu Koo Justyna Szyroka Neale Harrison Aditi Kanhere Michael G. Tomlinson Michael G. Tomlinson |
| author_facet | Alexandra L. Matthews Chek Ziu Koo Chek Ziu Koo Justyna Szyroka Neale Harrison Aditi Kanhere Michael G. Tomlinson Michael G. Tomlinson |
| author_sort | Alexandra L. Matthews |
| collection | DOAJ |
| description | A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane protein that functions as a “molecular scissor” to cleave the extracellular regions from its transmembrane target proteins. ADAM10 is well characterized as the ligand-dependent activator of Notch proteins, which control cell fate decisions. Indeed, conditional knockouts of ADAM10 in mice reveal impaired B-, T-, and myeloid cell development and/or function. ADAM10 cleaves many other leukocyte-expressed substrates. On B-cells, ADAM10 cleavage of the low-affinity IgE receptor CD23 promotes allergy and asthma, cleavage of ICOS ligand impairs antibody responses, and cleavage of the BAFF–APRIL receptor transmembrane activator and CAML interactor, and BAFF receptor, reduce B-cell survival. On microglia, increased ADAM10 cleavage of a rare variant of the scavenger receptor triggering receptor expressed on myeloid cells 2 may increase susceptibility to Alzheimer’s disease. We and others recently showed that ADAM10 interacts with one of six different regulatory tetraspanin membrane proteins, which we termed the TspanC8 subgroup, comprising Tspan5, Tspan10, Tspan14, Tspan15, Tspan17, and Tspan33. The TspanC8s are required for ADAM10 exit from the endoplasmic reticulum, and emerging evidence suggests that they dictate ADAM10 subcellular localization and substrate specificity. Therefore, we propose that ADAM10 should not be regarded as a single scissor, but as six different scissors with distinct substrate specificities, depending on the associated TspanC8. In this review, we collate recent transcriptomic data to present the TspanC8 repertoires of leukocytes, and we discuss the potential role of the six TspanC8/ADAM10 scissors in leukocyte development and function. |
| first_indexed | 2024-12-16T17:44:17Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T17:44:17Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-890bcc48acbb413dbf995531b5a520482022-12-21T22:22:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-07-01910.3389/fimmu.2018.01451387942Regulation of Leukocytes by TspanC8 Tetraspanins and the “Molecular Scissor” ADAM10Alexandra L. Matthews0Chek Ziu Koo1Chek Ziu Koo2Justyna Szyroka3Neale Harrison4Aditi Kanhere5Michael G. Tomlinson6Michael G. Tomlinson7School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United KingdomSchool of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United KingdomCentre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, United KingdomSchool of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United KingdomSchool of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United KingdomSchool of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United KingdomSchool of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, United KingdomCentre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, United KingdomA disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane protein that functions as a “molecular scissor” to cleave the extracellular regions from its transmembrane target proteins. ADAM10 is well characterized as the ligand-dependent activator of Notch proteins, which control cell fate decisions. Indeed, conditional knockouts of ADAM10 in mice reveal impaired B-, T-, and myeloid cell development and/or function. ADAM10 cleaves many other leukocyte-expressed substrates. On B-cells, ADAM10 cleavage of the low-affinity IgE receptor CD23 promotes allergy and asthma, cleavage of ICOS ligand impairs antibody responses, and cleavage of the BAFF–APRIL receptor transmembrane activator and CAML interactor, and BAFF receptor, reduce B-cell survival. On microglia, increased ADAM10 cleavage of a rare variant of the scavenger receptor triggering receptor expressed on myeloid cells 2 may increase susceptibility to Alzheimer’s disease. We and others recently showed that ADAM10 interacts with one of six different regulatory tetraspanin membrane proteins, which we termed the TspanC8 subgroup, comprising Tspan5, Tspan10, Tspan14, Tspan15, Tspan17, and Tspan33. The TspanC8s are required for ADAM10 exit from the endoplasmic reticulum, and emerging evidence suggests that they dictate ADAM10 subcellular localization and substrate specificity. Therefore, we propose that ADAM10 should not be regarded as a single scissor, but as six different scissors with distinct substrate specificities, depending on the associated TspanC8. In this review, we collate recent transcriptomic data to present the TspanC8 repertoires of leukocytes, and we discuss the potential role of the six TspanC8/ADAM10 scissors in leukocyte development and function.https://www.frontiersin.org/article/10.3389/fimmu.2018.01451/fulla disintegrin and metalloproteinase 10tetraspaninsTspanC8sleukocytes |
| spellingShingle | Alexandra L. Matthews Chek Ziu Koo Chek Ziu Koo Justyna Szyroka Neale Harrison Aditi Kanhere Michael G. Tomlinson Michael G. Tomlinson Regulation of Leukocytes by TspanC8 Tetraspanins and the “Molecular Scissor” ADAM10 Frontiers in Immunology a disintegrin and metalloproteinase 10 tetraspanins TspanC8s leukocytes |
| title | Regulation of Leukocytes by TspanC8 Tetraspanins and the “Molecular Scissor” ADAM10 |
| title_full | Regulation of Leukocytes by TspanC8 Tetraspanins and the “Molecular Scissor” ADAM10 |
| title_fullStr | Regulation of Leukocytes by TspanC8 Tetraspanins and the “Molecular Scissor” ADAM10 |
| title_full_unstemmed | Regulation of Leukocytes by TspanC8 Tetraspanins and the “Molecular Scissor” ADAM10 |
| title_short | Regulation of Leukocytes by TspanC8 Tetraspanins and the “Molecular Scissor” ADAM10 |
| title_sort | regulation of leukocytes by tspanc8 tetraspanins and the molecular scissor adam10 |
| topic | a disintegrin and metalloproteinase 10 tetraspanins TspanC8s leukocytes |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01451/full |
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