CoChat
Sign Up
Cited by 138Cell Adhesion Molecules ResearchProtease and Inhibitor MechanismsAlzheimer's disease research and treatments

TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization

Open access
Jouannet, Stéphanie, Saint-Pol, Julien, Fernandez, Laurent, Nguyen, Viet, Charrin, Stéphanie, Boucheix, Claude, Brou, Christel, Milhiet, Pierre-Emmanuel +1 more·2016·Cellular and Molecular Life Sciences
DOI 10.1007/s00018-015-2111-zPMC PMC4819958
Open this paper in CoChat — free accountOpen PDF

Abstract

The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N-cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co-immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s00018-015-2111-z

Cites

1 of 1 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • ADAM10 α-cleavage activity is influenced by growth factors, cytokines and neurotransmitters.

    “Post-translationally, ADAM10 α-cleavage activity is influenced by growth factors, cytokines and neurotransmitters”

    From GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein (2021) · cites this paper as [17]

    The Introduction (page unavailable) says ADAM10 activity can be stimulated by calcium ionophores, P2X7 receptor activation and antibodies against tetraspanins, supporting the general point that its cleavage activity is regulated. It does not identify growth factors, cytokines or neurotransmitters as regulators; it describes growth factors and cytokines as substrates of shedding. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Surface trafficking pathways mediated in part by tetraspanin proteins contribute to ADAM10 α-cleavage activity.

    “emerging studies indicate contributions of surface trafficking pathways that are mediated in part by tetraspanin proteins (15–17).”

    From GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein (2021) · cites this paper as [17]

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

Flagged first, then by citations

Research works printed but not linked: 51

  1. [1]Blobel CP ADAMs: key components in EGFR signalling and development Nat Rev Mol Cell Biol 2005 6 1 32 43 10.1038/nrm1548 15688065 · DOI
  2. [2]Saftig P Reiss K The “A Disintegrin And Metalloproteases” ADAM10 and ADAM17: novel drug targets with therapeutic potential? Eur J Cell Biol 2011 90 6–7 527 535 10.1016/j.ejcb.2010.11.005 21194787 · DOI
  3. [3]Lichtenthaler SF Alpha-secretase in Alzheimer’s disease: molecular identity, regulation and therapeutic potential J Neurochem 2011 116 1 10 21 10.1111/j.1471-4159.2010.07081.x 21044078 · DOI
  4. [4]Kopan R Ilagan MX The canonical Notch signaling pathway: unfolding the activation mechanism Cell 2009 137 2 216 233 10.1016/j.cell.2009.03.045 19379690 PMC2827930 · DOI
  5. [5]Bozkulak EC Weinmaster G Selective use of ADAM10 and ADAM17 in activation of Notch1 signaling Mol Cell Biol 2009 29 21 5679 5695 10.1128/MCB.00406-09 19704010 PMC2772745 · DOI
  6. [6]van Tetering G van Diest P Verlaan I van der WE Kopan R Vooijs M Metalloprotease ADAM10 is required for Notch1 site 2 cleavage J Biol Chem 2009 284 45 31018 31027 10.1074/jbc.M109.006775 19726682 PMC2781502 · DOI
  7. [7]Groot AJ Habets R Yahyanejad S Hodin CM Reiss K Saftig P Theys J Vooijs M Regulated proteolysis of NOTCH2 and NOTCH3 receptors by ADAM10 and presenilins Mol Cell Biol 2014 34 15 2822 2832 10.1128/MCB.00206-14 24842903 PMC4135574 · DOI
  8. [8]Hartmann D de Strooper B Serneels L Craessaerts K Herreman A Annaert W Umans L Lubke T Lena IA von Figura K Saftig P The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts Hum Mol Genet 2002 11 21 2615 2624 10.1093/hmg/11.21.2615 12354787 · DOI
  9. [9]Tian L Wu X Chi C Han M Xu T Zhuang Y ADAM10 is essential for proteolytic activation of Notch during thymocyte development Int Immunol 2008 20 9 1181 1187 10.1093/intimm/dxn076 18635581 · DOI
  10. [10]Jorissen E Prox J Bernreuther C Weber S Schwanbeck R Serneels L Snellinx A Craessaerts K Thathiah A Tesseur I Bartsch U Weskamp G Blobel CP Glatzel M De Strooper B Saftig P The disintegrin/metalloproteinase ADAM10 is essential for the establishment of the brain cortex J Neurosci 2010 30 14 4833 4844 10.1523/JNEUROSCI.5221-09.2010 20371803 PMC2921981 · DOI · Paper page
  11. [11]Glomski K Monette S Manova K De Strooper B Saftig P Blobel CP Deletion of Adam10 in endothelial cells leads to defects in organ-specific vascular structures Blood 2011 118 4 1163 1174 10.1182/blood-2011-04-348557 21652679 PMC3148163 · DOI
  12. [12]Horiuchi K Le Gall S Schulte M Yamaguchi T Reiss K Murphy G Toyama Y Hartmann D Saftig P Blobel CP Substrate selectivity of epidermal growth factor-receptor ligand sheddases and their regulation by phorbol esters and calcium influx Mol Biol Cell 2007 18 1 176 188 10.1091/mbc.E06-01-0014 17079736 PMC1751309 · DOI
  13. [13]Arduise C Abache T Li L Billard M Chabanon A Ludwig A Mauduit P Boucheix C Rubinstein E Le Naour F Tetraspanins regulate ADAM10-mediated cleavage of TNF-alpha and epidermal growth factor J Immunol 2008 181 10 7002 7013 10.4049/jimmunol.181.10.7002 18981120 · DOI
  14. [14]Le Gall SM Bobe P Reiss K Horiuchi K Niu XD Lundell D Gibb DR Conrad D Saftig P Blobel CP ADAMs 10 and 17 represent differentially regulated components of a general shedding machinery for membrane proteins such as transforming growth factor alpha, L-selectin, and tumor necrosis factor alpha Mol Biol Cell 2009 20 6 1785 1794 10.1091/mbc.E08-11-1135 19158376 PMC2655247 · DOI
  15. [15]Peschon JJ Slack JL Reddy P Stocking KL Sunnarborg SW Lee DC Russell WE Castner BJ Johnson RS Fitzner JN Boyce RW Nelson N Kozlosky CJ Wolfson MF Rauch CT Cerretti DP Paxton RJ March CJ Black RA An essential role for ectodomain shedding in mammalian development Science 1998 282 5392 1281 1284 10.1126/science.282.5392.1281 9812885 · DOI
  16. [16]Dornier E Coumailleau F Ottavi JF Moretti J Boucheix C Mauduit P Schweisguth F Rubinstein E TspanC8 tetraspanins regulate ADAM10/Kuzbanian trafficking and promote Notch activation in flies and mammals J Cell Biol 2012 199 3 481 496 10.1083/jcb.201201133 23091066 PMC3483123 · DOI
  17. [17]Dunn CD Sulis ML Ferrando AA Greenwald I A conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells Proc Natl Acad Sci U S A 2010 107 13 5907 5912 10.1073/pnas.1001647107 20220101 PMC2851858 · DOI
  18. [18]Haining EJ Yang J Bailey RL Khan K Collier R Tsai S Watson SP Frampton J Garcia P Tomlinson MG The TspanC8 subgroup of tetraspanins interacts with A disintegrin and metalloprotease 10 (ADAM10) and regulates its maturation and cell surface expression J Biol Chem 2012 287 47 39753 39765 10.1074/jbc.M112.416503 23035126 PMC3501075 · DOI · Paper page
  19. [19]Prox J Willenbrock M Weber S Lehmann T Schmidt-Arras D Schwanbeck R Saftig P Schwake M Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10 Cell Mol Life Sci 2012 69 17 2919 2932 10.1007/s00018-012-0960-2 22446748 PMC11114675 · DOI
  20. [20]Charrin S Jouannet S Boucheix C Rubinstein E Tetraspanins at a glance J Cell Sci 2014 127 Pt 17 3641 3648 10.1242/jcs.154906 25128561 · DOI
  21. [21]Charrin S Le Naour F Silvie O Milhiet PE Boucheix C Rubinstein E Lateral organization of membrane proteins: tetraspanins spin their web Biochem J 2009 420 2 133 154 10.1042/BJ20082422 19426143 · DOI
  22. [22]Hemler ME Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain Annu Rev Cell Dev Biol 2003 19 397 422 10.1146/annurev.cellbio.19.111301.153609 14570575 · DOI
  23. [23]Serru V Le Naour F Billard M Azorsa DO Lanza F Boucheix C Rubinstein E Selective Tetraspan/integrin complexes (CD81/α4β1, CD151/α3β1, CD151/α6β1) under conditions disrupting tetraspan interactions Biochem J 1999 340 103 111 10229664 PMC1220227
  24. [24]Yauch RL Berditchevski F Harler MB Reichner J Hemler ME Highly stoichiometric, stable, and specific association of integrin alpha3beta1 with CD151 provides a major link to phosphatidylinositol 4-kinase, and may regulate cell migration Mol Biol Cell 1998 9 2751 2765 10.1091/mbc.9.10.2751 9763442 PMC25552 · DOI
  25. [25]Charrin S Le Naour F Labas V Billard M Le Caer JP Emile JF Petit MA Boucheix C Rubinstein E EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells Biochem J 2003 373 409 421 10.1042/bj20030343 12708969 PMC1223506 · DOI
  26. [26]Stipp CS Kolesnikova TV Hemler ME EWI-2 Is a Major CD9 and CD81 Partner and Member of a Novel Ig Protein Subfamily J Biol Chem 2001 276 44 40545 40554 10.1074/jbc.M107338200 11504738 · DOI
  27. [27]Stipp CS Orlicky D Hemler ME FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein J Biol Chem 2001 276 7 4853 4862 10.1074/jbc.M009859200 11087758 · DOI
  28. [28]Charrin S Le Naour F Oualid M Billard M Faure G Hanash SM Boucheix C Rubinstein E The major CD9 and CD81 molecular partner: identification and characterization of the complexes J Biol Chem 2001 276 14329 14337 11278880
  29. [29]Yanez-Mo M Barreiro O Gordon-Alonso M Sala-Valdes M Sanchez-Madrid F Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes Trends Cell Biol 2009 19 9 434 446 10.1016/j.tcb.2009.06.004 19709882 · DOI
  30. [30]Jarriault S Brou C Logeat F Schroeter EH Kopan R Israel A Signalling downstream of activated mammalian Notch Nature 1995 377 6547 355 358 10.1038/377355a0 7566092 · DOI
  31. [31]Schroeter EH Kisslinger JA Kopan R Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain Nature 1998 393 6683 382 386 10.1038/30756 9620803 · DOI
  32. [32]Mumm JS Schroeter EH Saxena MT Griesemer A Tian X Pan DJ Ray WJ Kopan R A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1 Mol Cell 2000 5 2 197 206 10.1016/S1097-2765(00)80416-5 10882062 · DOI
  33. [33]Bin Hafeez B Adhami VM Asim M Siddiqui IA Bhat KM Zhong W Saleem M Din M Setaluri V Mukhtar H Targeted knockdown of Notch1 inhibits invasion of human prostate cancer cells concomitant with inhibition of matrix metalloproteinase-9 and urokinase plasminogen activator Clin Cancer Res 2009 15 2 452 459 10.1158/1078-0432.CCR-08-1631 19147749 PMC2951134 · DOI
  34. [34]Espenel C Margeat E Dosset P Arduise C Le Grimellec C Royer CA Boucheix C Rubinstein E Milhiet PE Single-molecule analysis of CD9 dynamics and partitioning reveals multiple modes of interaction in the tetraspanin web J Cell Biol 2008 182 4 765 776 10.1083/jcb.200803010 18710926 PMC2518714 · DOI
  35. [35]Krementsov DN Rassam P Margeat E Roy NH Schneider-Schaulies J Milhiet PE Thali M HIV-1 assembly differentially alters dynamics and partitioning of tetraspanins and raft components Traffic 2010 11 11 1401 1414 10.1111/j.1600-0854.2010.01111.x 20727121 PMC4073295 · DOI
  36. [36]Potel J Rassam P Montpellier C Kaestner L Werkmeister E Tews BA Couturier C Popescu CI Baumert TF Rubinstein E Dubuisson J Milhiet PE Cocquerel L EWI-2wint promotes CD81 clustering that abrogates Hepatitis C Virus entry Cell Microbiol 2013 15 7 1234 1252 10.1111/cmi.12112 23351194 PMC7162402 · DOI
  37. [37]Berditchevski F Odintsova E Characterization of integrin-tetraspanin adhesion complexes: role of tetraspanins in integrin signaling J Cell Biol 1999 146 2 477 492 10.1083/jcb.146.2.477 10427099 PMC2156181 · DOI
  38. [38]Charrin S Manie S Billard M Ashman L Gerlier D Boucheix C Rubinstein E Multiple levels of interactions within the tetraspanin web Biochem Biophys Res Commun 2003 304 1 107 112 10.1016/S0006-291X(03)00545-X 12705892 · DOI
  39. [39]Gambin Y Lopez-Esparza R Reffay M Sierecki E Gov NS Genest M Hodges RS Urbach W Lateral mobility of proteins in liquid membranes revisited Proc Natl Acad Sci U S A 2006 103 7 2098 2102 10.1073/pnas.0511026103 16461891 PMC1413751 · DOI
  40. [40]Guigas G Weiss M Size-dependent diffusion of membrane inclusions Biophys J 2006 91 7 2393 2398 10.1529/biophysj.106.087031 16829562 PMC1562383 · DOI
  41. [41]Masson JB Dionne P Salvatico C Renner M Specht CG Triller A Dahan M Mapping the energy and diffusion landscapes of membrane proteins at the cell surface using high-density single-molecule imaging and Bayesian inference: application to the multiscale dynamics of glycine receptors in the neuronal membrane Biophys J 2014 106 1 74 83 10.1016/j.bpj.2013.10.027 24411239 PMC3907207 · DOI
  42. [42]Cherukuri A Shoham T Sohn HW Levy S Brooks S Carter R Pierce SK The tetraspanin CD81 is necessary for partitioning of coligated CD19/CD21-B cell antigen receptor complexes into signaling-active lipid rafts J Immunol 2004 172 1 370 380 10.4049/jimmunol.172.1.370 14688345 · DOI
  43. [43]Berditchevski F Odintsova E Sawada S Gilbert E Expression of the palmitoylation-deficient CD151 weakens the association of alpha 3 beta 1 integrin with the tetraspanin-enriched microdomains and affects integrin-dependent signaling J Biol Chem 2002 277 40 36991 37000 10.1074/jbc.M205265200 12110679 · DOI
  44. [45]Yang XH Mirchev R Deng X Yacono P Yang HL Golan DE Hemler ME CD151 restricts the alpha6 integrin diffusion mode J Cell Sci 2012 125 Pt 6 1478 1487 10.1242/jcs.093963 22328509 PMC3336378 · DOI
  45. [46]Mattila PK Feest C Depoil D Treanor B Montaner B Otipoby KL Carter R Justement LB Bruckbauer A Batista FD The actin and tetraspanin networks organize receptor nanoclusters to regulate B cell receptor-mediated signaling Immunity 2013 38 3 461 474 10.1016/j.immuni.2012.11.019 23499492 · DOI
  46. [47]Moretti J Chastagner P Gastaldello S Heuss SF Dirac AM Bernards R Masucci MG Israel A Brou C The translation initiation factor 3f (eIF3f) exhibits a deubiquitinase activity regulating Notch activation PLoS Biol 2010 8 11 e1000545 10.1371/journal.pbio.1000545 21124883 PMC2990700 · DOI
  47. [48]Sincock PM Fitter S Parton RG Berndt MC Gamble JR Ashman LK PETA-3/CD151, a member of the transmembrane 4 superfamily, is localised to the plasma membrane and endocytic system of endothelial cells, associates with multiple integrins and modulates cell function J Cell Sci 1999 112 833 844 10036233
  48. [49]Sachs N Kreft M van den Bergh Weerman MA Beynon AJ Peters TA Weening JJ Sonnenberg A Kidney failure in mice lacking the tetraspanin CD151 J Cell Biol 2006 175 1 33 39 10.1083/jcb.200603073 17015618 PMC2064491 · DOI
  49. [50]Six EM Ndiaye D Sauer G Laabi Y Athman R Cumano A Brou C Israel A Logeat F The notch ligand Delta1 recruits Dlg1 at cell-cell contacts and regulates cell migration J Biol Chem 2004 279 53 55818 55826 10.1074/jbc.M408022200 15485825 · DOI
  50. [51]Grassi G Maccaroni P Meyer R Kaiser H D’Ambrosio E Pascale E Grassi M Kuhn A Di Nardo P Kandolf R Kupper JH Inhibitors of DNA methylation and histone deacetylation activate cytomegalovirus promoter-controlled reporter gene expression in human glioblastoma cell line U87 Carcinogenesis 2003 24 10 1625 1635 10.1093/carcin/bgg118 12869421 · DOI
  51. [52]Hicks C Johnston SH diSibio G Collazo A Vogt TF Weinmaster G Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2 Nat Cell Biol 2000 2 8 515 520 10.1038/35019553 10934472 · DOI

Cited by

Sorted by citations

Authors
Jouannet, S., Saint-Pol, J., Fernandez, L., Nguyen, V., Charrin, S., Boucheix, C., Brou, C., Milhiet, P.-E., & Rubinstein, E.
Affiliations
  • Université Paris-Sud (FR)
  • Centre National de la Recherche Scientifique (FR)
  • Institut Pasteur (FR)
Corresponding author
Rubinstein, Eric
ORCID
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
2015-12-19
Volume
73
Issue
9
Pages
1895-1915
ISSN
  • 1420-682X (ISSN-L)
  • 1420-9071
DOI
10.1007/s00018-015-2111-z
PMC
PMC4819958
OpenAlex
W2260460109
Cited by
138
References
1
Citations by year
2026: 10 · 2025: 7 · 2024: 20 · 2023: 15 · 2022: 14 · 2021: 11 · 2020: 12 · 2019: 10 · 2018: 13 · 2017: 14 · 2016: 12
FWCI
11.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Life Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Association pour la Recherche sur le Cancer (FR)
  • Institut National du cancer (INCA)
  • NRB-Vaincre le Cancer
  • Institut du Cancer et d’Immunogénétique
  • Institut National Du Cancer
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 › Physiology › Alzheimer's disease research and treatments
Keywords
ADAM10, tetraspanins, N-cadherin, CD44, proteolytic cleavage, membrane compartmentalization, endoplasmic reticulum exit, amyloid precursor protein, single-molecule tracking
MeSH terms
ADAM10 Protein, Chromatography, High Pressure Liquid, Humans, Membrane Proteins, Substrate Specificity, Cadherins, Amyloid beta-Protein Precursor, Microscopy, Confocal, Hyaluronan Receptors, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Immunoprecipitation, ADAM Proteins, Receptor, Notch1, Tandem Mass Spectrometry, Amyloid Precursor Protein Secretases, Tetraspanins

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