The TspanC8 Subgroup of Tetraspanins Interacts with A Disintegrin and Metalloprotease 10 (ADAM10) and Regulates Its Maturation and Cell Surface Expression
Open accessAbstract
A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitous transmembrane metalloprotease that cleaves the extracellular regions from over 40 different transmembrane target proteins, including Notch and amyloid precursor protein. ADAM10 is essential for embryonic development and is also important in inflammation, cancer, and Alzheimer disease. However, ADAM10 regulation remains poorly understood. ADAM10 is compartmentalized into membrane microdomains formed by tetraspanins, which are a superfamily of 33 transmembrane proteins in humans that regulate clustering and trafficking of certain other transmembrane "partner" proteins. This is achieved by specific tetraspanin-partner interactions, but it is not clear which tetraspanins specifically interact with ADAM10. The aims of this study were to identify which tetraspanins interact with ADAM10 and how they regulate this metalloprotease. Co-immunoprecipitation identified specific ADAM10 interactions with Tspan5, Tspan10, Tspan14, Tspan15, Tspan17, and Tspan33/Penumbra. These are members of the largely unstudied TspanC8 subgroup of tetraspanins, all six of which promoted ADAM10 maturation. Different cell types express distinct repertoires of TspanC8 tetraspanins. Human umbilical vein endothelial cells express relatively high levels of Tspan14, the knockdown of which reduced ADAM10 surface expression and activity. Mouse erythrocytes express predominantly Tspan33, and ADAM10 expression was substantially reduced in the absence of this tetraspanin. In contrast, ADAM10 expression was normal on Tspan33-deficient mouse platelets in which Tspan14 is the major TspanC8 tetraspanin. These results define TspanC8 tetraspanins as essential regulators of ADAM10 maturation and trafficking to the cell surface. This finding has therapeutic implications because focusing on specific TspanC8-ADAM10 complexes may allow cell type- and/or substrate-specific ADAM10 targeting.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
TSPAN14 and TSPAN10 code for tetraspanins in the TspanC8 subgroup, which promote ADAM10 maturation.
“These two genes code for tetraspanins that are a part of the TspanC8 subgroup of tetraspanins which promote ADAM10 maturation [47].”
From Genetic associations with age at dementia onset in the <i>PSEN1 E280A</i> Colombian kindred (2023) · cites this paper as [47]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega
Sievers, F., Wilm, A., Dineen, D., Gibson, T., Karplus, K., Li, W.-Z., Lopez, R., McWilliam, H., Remmert, M., Söding, J., et al. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.75 · Cited by 15,576 · see citing works
The β-Catenin/TCF-4 Complex Imposes a Crypt Progenitor Phenotype on Colorectal Cancer Cells
van de Wetering, M., Sancho, E., Verweij, C., de Lau, W., Oving, I., Hurlstone, A., van der Horn, K., Batlle, E., Coudreuse, D., Haramis, A.-P., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)01014-0 · Cited by 2,030 · see citing works
Lammich, S., Kojro, E., Postina, R., Gilbert, S., Pfeiffer, R., Jasionowski, M., Haass, C., & Fahrenholz, F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3922 · Cited by 1,132 · see citing works
Maciag, T., Cerundolo, J., Ilsley, S., Kelley, P. R., & Forand, R. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.11.5674 · Cited by 704 · see citing works
Hartmann, D. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.21.2615 · Cited by 680 · see citing works
Postina, R., Schroeder, A., Dewachter, I., Bohl, J., Schmitt, U., Kojro, E., Prinzen, C., Endres, K., Hiemke, C., Blessing, M., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20864 · Cited by 638 · see citing works
Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes
Yáñez‐Mó, M., Barreiro, O., Gordón‐Alonso, M., Sala-Valdés, M., & Sánchez‐Madrid, F. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2009.06.004 · Cited by 617 · see citing works
Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes
Rowley, J. W., Oler, A. J., Tolley, N. D., Hunter, B. N., Low, E. N., Nix, D. A., Yost, C. C., Zimmerman, G. A., & Weyrich, A. S. (2011) · Blood · doi:10.1182/blood-2011-03-339705 · Cited by 562 · see citing works
Lateral organization of membrane proteins: tetraspanins spin their web
Charrin, S., Naour, F. L., Silvie, O., Milhiet, P., Boucheix, C., & Rubinstein, E. (2009) · Biochemical Journal · doi:10.1042/bj20082422 · Cited by 440 · see citing works
Junge, H. J., Yang, S. C., Burton, J. B., Paes, K., Shu, X., French, D. M., Costa, M., Rice, D. S., & Ye, W. (2009) · Cell · doi:10.1016/j.cell.2009.07.048 · Cited by 391 · see citing works
CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency
van Zelm, M. C., Smet, J., Adams, B., Mascart, F., Schandené, L., Janssen, F., Ferster, A., Kuo, C.-C., Levy, S., van Dongen, J. J. M., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39748 · Cited by 380 · see citing works
Schulz, B., Pruessmeyer, J., Maretzky, T., Ludwig, A., Blobel, C., Säftig, P., & Reiß, K. (2008) · Circulation Research · doi:10.1161/circresaha.107.169805 · Cited by 301 · see citing works
Säftig, P., & Reiß, K. (2010) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2010.11.005 · Cited by 298 · see citing works
Controlled shedding of platelet glycoprotein (GP)VI and GPIb–IX–V by ADAM family metalloproteinases
Gardiner, E. E., Karunakaran, D., SHEN, Y., Arthur, J. F., Andrews, R. K., & Berndt, M. C. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02590.x · Cited by 271 · see citing works
Michelsen, K., Yuan, H., & Schwappach, B. (2005) · The EMBO Reports · doi:10.1038/sj.embor.7400480 · Cited by 235 · see citing works
A physical and functional link between cholesterol and tetraspanins
Charrin, S., Manié, S. N., Thiele, C., Billard, M., Gerlier, D., Boucheix, C., & Rubinstein, E. (2003) · European Journal of Immunology · doi:10.1002/eji.200323884 · Cited by 232 · see citing works
Nikopoulos, K., Gilissen, C., Hoischen, A., Nouhuys, C. E. V., Boonstra, F. N., Blokland, E. A. W., Arts, P., Wieskamp, N., Strom, T. M., Ayuso, C., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.12.016 · Cited by 228 · see citing works
Barreiro, O., Zamai, M., Yáñez‐Mó, M., Tejera, E., López‐Romero, P., Monk, P. N., Gratton, E., Caiolfa, V. R., & Sánchez‐Madrid, F. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200805076 · Cited by 219 · see citing works
The role of ADAM-mediated shedding in vascular biology
Yildiz, D., Pruessmeyer, J., Groth, E., & Ludwig, A. (2011) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2011.09.003 · Cited by 208 · see citing works
Sincock, P. M., Mayrhofer, G., & Ashman, L. K. (1997) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215549704500404 · Cited by 193 · see citing works
Mutations in TSPAN12 Cause Autosomal-Dominant Familial Exudative Vitreoretinopathy
Poulter, J. A., Ali, M., Gilmour, D. F., Rice, A., Kondo, H., Hayashi, K., Mackey, D. A., Kearns, L. S., Ruddle, J. B., Craig, J. E., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.01.012 · Cited by 193 · see citing works
Hundhausen, C., Schulte, A., Schulz, B., Andrzejewski, M. G., Schwarz, N., von Hundelshausen, P., Winter, U., Paliga, K., Reiß, K., Säftig, P., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.12.8064 · Cited by 178 · see citing works
Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro
Takeda, Y., Kazarov, A. R., Butterfield, C., Hopkins, B. D., Benjamin, L. E., Kaipainen, A., & Hemler, M. E. (2006) · Blood · doi:10.1182/blood-2006-08-041970 · Cited by 167 · see citing works
Polyethylenimine, a cost‐effective transfection reagent
Ehrhardt, C., Schmolke, M., Matzke, A., et al. (2006) · Signal Transduction · doi:10.1002/sita.200500073 · Cited by 160 · see citing works
Tetraspanins Regulate ADAM10-Mediated Cleavage of TNF-α and Epidermal Growth Factor
Arduise, C., Abache, T., Li, L., Billard, M., Chabanon, A., Ludwig, A., Mauduit, P., Boucheix, C., Rubinstein, E., & Naour, F. L. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.10.7002 · Cited by 154 · see citing works
Platelet membrane proteomics: a novel repository for functional research
Lewandrowski, U., Wortelkamp, S., Lohrig, K., et al. (2009) · Blood · doi:10.1182/blood-2009-02-203828 · Cited by 133 · see citing works
Tetraspanin12 regulates ADAM10‐dependent cleavage of amyloid precursor protein
Xu, D., Sharma, C., & Hemler, M. E. (2009) · The FASEB Journal · doi:10.1096/fj.09-133462 · Cited by 130 · see citing works
Differentially regulated GPVI ectodomain shedding by multiple platelet–expressed proteinases
Bender, M., Hofmann, S., Stegner, D., Chalaris, A., Bösl, M. R., Braun, A., Scheller, J., Rose‐John, S., & Nieswandt, B. (2010) · Blood · doi:10.1182/blood-2010-06-289108 · Cited by 128 · see citing works
Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10
Prox, J., Willenbrock, M., Weber, S., Lehmann, T., Schmidt‐Arras, D., Schwanbeck, R., Säftig, P., & Schwake, M. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0960-2 · Cited by 114 · see citing works
Donners, M. M. P. C., Wolfs, I. M. J., Olieslagers, S., Mohammadi-Motahhari, Z., Tchaikovski, V., Heeneman, S., van Buul, J. D., Caolo, V., Molin, D. G. M., Post, M. J., et al. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.213124 · Cited by 105 · see citing works
Coordination of erythropoiesis by the transcription factor c-Myb
Vegiopoulos, A., García, P., Emambokus, N. R., & Frampton, J. (2006) · Blood · doi:10.1182/blood-2005-07-2968 · Cited by 103 · see citing works
Self-citationImpaired “outside-in” integrin αIIbβ3 signaling and thrombus stability in TSSC6-deficient mice
Goschnick, M. W., Lau, L.-M., Wee, J. L. K., et al. (2006) · Blood · doi:10.1182/blood-2006-02-004267 · Cited by 91 · see citing works
CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin
Doyle, E. L., Ridger, V. C., Ferraro, F., et al. (2011) · Blood · doi:10.1182/blood-2010-11-321489 · Cited by 90 · see citing works
Deletion of Adam10 in endothelial cells leads to defects in organ-specific vascular structures
Glomski, K., Monette, S., Manova, K., et al. (2011) · Blood · doi:10.1182/blood-2011-04-348557 · Cited by 84 · see citing works
Takeda, Y., He, P., Tachibana, I., Zhou, B., Miyado, K., Kaneko, H., Suzuki, M., Minami, S., Iwasaki, T., Goya, S., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801902200 · Cited by 83 · see citing works
Orlowski, E., Chand, R., Yip, J., et al. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03612.x · Cited by 79 · see citing works
Protty, M. B., Watkins, N. A., Colombo, D., Thomas, S. G., Heath, V. L., Herbert, J. M. J., Bicknell, R., Senis, Y. A., Ashman, L. K., Berditchevski, F., et al. (2008) · Biochemical Journal · doi:10.1042/bj20081126 · Cited by 73 · see citing works
Self-citationAdam10 is essential for early embryonic cardiovascular development
Zhang, C., Tian, L., Chi, C., Wu, X., Yang, X. Y., Han, M., Xu, T., Zhuang, Y., & Deng, K. (2010) · Developmental Dynamics · doi:10.1002/dvdy.22391 · Cited by 67 · see citing works
Tomlinson, M. G., Woods, D. B., McMahon, M., Wahl, M. I., Witte, O. N., Kurosaki, T., Bolen, J. B., & Johnston, J. A. (2001) · BMC Immunology · doi:10.1186/1471-2172-2-4 · Cited by 65 · see citing works
Self-citationAn Arginine Stretch Limits ADAM10 Exit from the Endoplasmic Reticulum
Marcello, E. E., Gardoni, F., Luca, M. D., & Pérez‐Otaño, I. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.055947 · Cited by 65 · see citing works
McCarty, O. J. T., Calaminus, S. D. J., Berndt, M. C., et al. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01966.x · Cited by 55 · see citing works
Heikens, M. J., Cao, T. M., Morita, C., DeHart, S. L., & Tsai, S. (2006) · Blood · doi:10.1182/blood-2006-09-046672 · Cited by 29 · see citing works
Self-citationJackson, D. E., Lau, L.-M., Goschnick, M. W., et al. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.tb02043.x · Cited by 25 · see citing works
Platelet tetraspanins: small but interesting
Tomlinson, M. G. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03613.x · Cited by 23 · see citing works
Self-citationDumon, S., Heath, V. L., Tomlinson, M. G., Göttgens, B., & Frampton, J. (2006) · Experimental Hematology · doi:10.1016/j.exphem.2006.01.014 · Cited by 20 · see citing works
Self-citationTetraspanin microdomains: fine-tuning platelet function
Haining, E. J., Yang, J., & Tomlinson, M. G. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390518 · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Functional characterization of Alzheimer’s disease genetic variants in microglia
Yang, X., Wen, J., Yang, H., Jones, I. R., Zhu, X., Liu, W., Li, B., Clelland, C. D., Luo, W., Wong, M. Y., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01506-8 · Cited by 71 · see citing works
Genetic associations with age at dementia onset in the <i>PSEN1 E280A</i> Colombian kindred
Cochran, J. N., Acosta‐Uribe, J., Esposito, B. T., Madrigal, L., Aguillón, D., Giraldo, M. M., Taylor, J. W., Bradley, J., Fulton‐Howard, B., Andrews, S. J., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13021 · Cited by 21 · see citing works
- Authors
- Haining, E. J., Yang, J., Bailey, R. L., Khan, K., Collier, R., Tsai, S., Watson, S. P., Frampton, J., Garcia, P., & Tomlinson, M. G.
- Affiliations
- University of Birmingham (GB)
- University of Utah (US)
- Corresponding author
- Tomlinson, Michael G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 287
- Issue
- 47
- Pages
- 39753-39765
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3501075
- OpenAlex
- W2124744205
- Cited by
- 163
- References
- 46
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 10 · 2021: 9 · 2020: 17 · 2019: 15 · 2018: 16 · 2017: 15 · 2016: 18 · 2015: 14 · 2014: 7 · 2013: 6
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Funders
- British Heart Foundation (FS/08/062/25797)
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- ADAM10, tetraspanins, protein maturation, cell surface trafficking, lipid rafts, endothelial cells, erythrocytes, platelets, APP processing
- MeSH terms
- ADAM10 Protein, Alzheimer Disease, Animals, Blood Platelets, Cell Line, Erythrocytes, Humans, Inflammation, Membrane Proteins, Neoplasms, Protein Binding, Gene Expression Regulation, Enzymologic, Mice, Knockout, Protein Transport, Membrane Microdomains, Mice, ADAM Proteins, Amyloid Precursor Protein Secretases, Tetraspanins, Human Umbilical Vein Endothelial Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
