PreprintCited by 2Cell Adhesion Molecules ResearchSkin and Cellular Biology ResearchBiotin and Related Studies

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The Desmoglein 2 interactome in primary neonatal cardiomyocytes

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Preprint — published as 10.1242/jcs.264213 · Paper page

Abstract

Mechanical coupling and chemical communication between cardiomyocytes are facilitated through a specialized adhesive structure known as the intercalated disc (ICD). The ICD is essential for heart organization and contraction. Yet, the network of adhesion, adaptor, and signaling proteins that form the ICD remains poorly defined. Here, we combined proximity labeling and quantitative mass spectrometry to identify proteins associated with the desmosomal cadherin, Desmoglein 2 (DSG2), in cultured neonatal cardiomyocytes. We identified over 300 proteins in the DSG2 interactome; half of which are shared with the N-cadherin (CDH2) interactome in cardiomyocytes. Proteins unique to DSG2 include the gap junction protein connexin 43 and the plakin family of cytolinker proteins. Comparison of the cardiomyocyte DSG2 interactome with the interactomes of desmosomal proteins from epithelia revealed only a small number of shared proteins. In cardiomyocytes, plakoglobin (JUP) and plakophilin 2 (PKP2) were the most abundant shared proteins between the DSG2 and CDH2 interactomes. PKP2 is a dynamic protein whose membrane recruitment in cardiomyocytes is tension-dependent. Our analysis of the DSG2 interactome provides a critical new dimension to the proteomic atlas of the essential molecular complexes required for cardiomyocyte adhesion.

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Research works printed but not linked: 77

  1. 10.1016/j.jmb.2013.07.035 · DOI
  2. 10.1016/S0955-0674(00)00258-1 · DOI
  3. Baddam, S.R. , P.T. Arsenovic , V. Narayanan , N.R. Duggan , C.R. Mayer , S.T. Newman , D.A. Abutaleb , A. Mohan , A.P. Kowalczyk , and D.E. Conway . 2018. The Desmosomal Cadherin Desmoglein-2 Experiences Mechanical Tension as Demonstrated by a FRET-Based Tension Biosensor Expressed in Living Cells. Cells. 7. · DOI
  4. 10.1091/mbc.E19-09-0542 · DOI
  5. Bartle, E.I. , T.C. Rao , R.R. Beggs , W.F. Dean , T.M. Urner , A.P. Kowalczyk , and A.L. Mattheyses . 2020. Protein exchange is reduced in calcium-independent epithelial junctions. J Cell Biol. 219. · DOI
  6. 10.1016/j.ceb.2009.07.002 · DOI
  7. 10.1080/21688370.2021.2017225 · DOI
  8. Bharathan, N.K. , A.L. Mattheyses , and A.P. Kowalczyk . 2024. The desmosome comes into focus. J Cell Biol. 223. · DOI
  9. 10.1038/jid.2009.390 · DOI
  10. 10.1083/jcb.200303036 · DOI
  11. 10.1016/j.ejcb.2006.02.009 · DOI
  12. 10.1038/nbt.4201 · DOI · Paper page
  13. Broussard, J.A. , A. Jaiganesh , H. Zarkoob , D.E. Conway , A.R. Dunn , H.D. Espinosa , P.A. Janmey , and K.J. Green . 2020. Scaling up single-cell mechanics to multicellular tissues - the role of the intermediate filament-desmosome network. J Cell Sci. 133. · DOI
  14. 10.1038/s41580-023-00688-7 · DOI · Paper page
  15. 10.1074/jbc.M108765200 · DOI
  16. 10.1074/jbc.M109.047928 · DOI
  17. 10.1073/pnas.1203906109 · DOI
  18. 10.1038/nbt.1511 · DOI · Paper page
  19. 10.1038/ejhg.2010.19 · DOI
  20. 10.1161/CIRCRESAHA.110.223412 · DOI
  21. Ehler, E. , T. Moore-Morris , and S. Lange . 2013. Isolation and culture of neonatal mouse cardiomyocytes. J Vis Exp. · DOI
  22. 10.1249/MSS.0000000000003464 · DOI
  23. 10.1016/j.ejcb.2005.11.003 · DOI
  24. 10.1016/j.ejcb.2006.11.003 · DOI
  25. 10.1016/j.bpj.2022.02.023 · DOI
  26. 10.1016/j.mcpro.2024.100735 · DOI
  27. Fulle, J.B. , H. Huppert , D. Liebl , J. Liu , R. Alves de Almeida , B. Yanes , G.D. Wright , E.B. Lane , D.R. Garrod , and C. Ballestrem . 2021. Desmosome dualism - most of the junction is stable, but a plakophilin moiety is persistently dynamic. J Cell Sci. 134. · DOI
  28. 10.1242/jcs.004713 · DOI
  29. Guo, Z. , L.J. Neilson , H. Zhong , P.S. Murray , S. Zanivan , and R. Zaidel-Bar . 2014. E-cadherin interactome complexity and robustness resolved by quantitative proteomics. Science signaling. 7:rs7. · DOI
  30. 10.3109/15419061.2013.855204 · DOI
  31. 10.1073/pnas.1606272113 · DOI
  32. 10.3109/15419061.2013.876017 · DOI
  33. 10.1073/pnas.95.5.2509 · DOI
  34. 10.1016/j.devcel.2022.11.010 · DOI
  35. 10.1016/j.jbc.2021.100582 · DOI
  36. 10.1186/1471-2164-9-488 · DOI
  37. 10.1016/j.jmb.2008.12.054 · DOI
  38. 10.1161/CIRCGENETICS.114.000974 · DOI
  39. 10.1007/s00441-011-1322-3 · DOI
  40. 10.1091/mbc.E15-12-0844 · DOI
  41. 10.1016/B978-0-12-394311-8.00005-4 · DOI · Paper page
  42. 10.1007/s00395-011-0175-y · DOI
  43. Le, S. , M. Yu , and J. Yan . 2019. Direct single-molecule quantification reveals unexpectedly high mechanical stability of vinculin-talin/alpha-catenin linkages. Sci Adv. 5:eaav2720. · DOI
  44. 2016, Proximity-Dependent Biotinylation for Identification of Interacting Proteins, Current protocols in cell biology / editorial board, Juan S. Bonifacino, 73, 17 19 11
  45. 10.1016/S0962-8924(01)02180-8 · DOI
  46. 10.1242/jcs.098640 · DOI
  47. 10.3389/fphys.2020.612927 · DOI
  48. Li, Y. , C.D. Merkel , X. Zeng , J.A. Heier , P.S. Cantrell , M. Sun , D.B. Stolz , S.C. Watkins , N.A. Yates , and A.V. Kwiatkowski . 2019. The N-cadherin interactome in primary cardiomyocytes as defined using quantitative proximity proteomics. J Cell Sci. 132. · DOI · Paper page
  49. 10.1038/nprot.2007.135 · DOI
  50. Maki, K. , S.W. Han , Y. Hirano , S. Yonemura , T. Hakoshima , and T. Adachi . 2018. Real-time TIRF observation of vinculin recruitment to stretched alpha-catenin by AFM. Sci Rep-Uk. 8. · DOI
  51. 10.1091/mbc.E19-04-0216 · DOI
  52. 10.1016/j.bpj.2012.02.029 · DOI
  53. 10.1016/j.tcb.2013.06.004 · DOI
  54. 10.1152/physrev.00021.2022 · DOI
  55. 10.1098/rsob.240208 · DOI
  56. 10.1091/mbc.E19-02-0102 · DOI
  57. 10.1016/S0021-9258(18)99244-6 · DOI
  58. 10.1002/pro.5217 · DOI
  59. 10.1084/jem.20090641 · DOI · Paper page
  60. 10.1007/s12551-020-00737-x · DOI
  61. Rubsam, M. , J.A. Broussard , S.A. Wickstrom , O. Nekrasova , K.J. Green , and C.M. Niessen . 2018. Adherens Junctions and Desmosomes Coordinate Mechanics and Signaling to Orchestrate Tissue Morphogenesis and Function: An Evolutionary Perspective. Cold Spring Harbor perspectives in biology. 10. · DOI
  62. 10.1091/mbc.E17-04-0231 · DOI
  63. Shafraz, O. , M. Rubsam , S.N. Stahley , A.L. Caldara , A.P. Kowalczyk , C.M. Niessen , and S. Sivasankar . 2018. E-cadherin binds to desmoglein to facilitate desmosome assembly. eLife. 7. · DOI
  64. 10.1073/pnas.2010209117 · DOI
  65. 10.1021/bi047881x · DOI
  66. 10.1073/pnas.91.23.10790 · DOI
  67. 10.1038/nprot.2016.136 · DOI
  68. 10.1093/nar/gkq1020 · DOI
  69. 10.1093/eurheartj/ehs373 · DOI
  70. 10.1242/jcs.140475 · DOI
  71. 10.1016/j.nmd.2014.09.011 · DOI
  72. 10.3109/15419061.2014.908853 · DOI
  73. 10.1038/ncomms5525 · DOI
  74. 10.1111/joa.13634 · DOI
  75. 10.1038/ncb2055 · DOI · Paper page
  76. 10.1016/j.biopha.2023.115448 · DOI
  77. 10.1093/cvr/cvy061 · DOI

Metadata

Authors
Li, Y., Campbell, A. P., Balasubramanian, S., Zeng, X., Porter, E., Cantrell, P. S., Sun, M., Mattheyses, A. S., & Kwiatkowski, A. V.
Affiliations
  • University of Pittsburgh (US)
  • Department of Cell, Developmental, and Integrative Biology, The University of Alabama at Birmingham, Birmingham, AL, USA
Corresponding author
Kwiatkowski, Adam V.
Venue
Journal of Cell Science
Publisher
openRxiv
Published
2025-06-10
Volume
139
Issue
3
ISSN
0021-9533 (ISSN-L)
OpenAlex
W7128019313
Cited by
2
References
1
Citations by year
2026: 1 · 2025: 1
FWCI
4.53
Type
journal article
Language
en
Open access
Locations
  • Journal of Cell Science (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by-nc-nd)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • American Heart Association
  • University of Pittsburgh
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL127711)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR072697)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
Keywords
desmoglein 2, desmosomes, intercalated discs, cardiomyocyte adhesion, protein-protein interaction network, N-cadherin, connexin 43, plakoglobin, plakophilin-2, desmosomal cadherins, mechanical tension, membrane recruitment, neonatal cardiomyocytes

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