The desmoglein 2 interactome in primary neonatal cardiomyocytes
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Abstract
Mechanical coupling and chemical communication between cardiomyocytes are facilitated through a specialized adhesive structure called 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 connexin 43 and the plakin family of cytolinker proteins. Comparison of the cardiomyocyte DSG2 interactome with the interactomes of desmosomal proteins from epithelia revealed few shared proteins. In cardiomyocytes, plakoglobin and plakophilin 2 (PKP2) were the most abundant shared proteins between the DSG2 and CDH2 interactomes. We show that PKP2 is a dynamic protein whose membrane recruitment in cardiomyocytes is dependent on tension. Our analysis of the DSG2 interactome provides a crucial new dimension to the proteomic atlas of the essential molecular complexes required for cardiomyocyte adhesion.
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Actomyosin forces trigger a conformational change in desmoplakin within desmosomes
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- Authors
- Li, Y., Campbell, A. P., Balasubramanian, S., Zeng, X., Porter, E., Cantrell, P. S., Sun, M., Mattheyses, A. L., & Kwiatkowski, A. V.
- Affiliations
- University of Pittsburgh (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Kwiatkowski, Adam V.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2026-02-01
- Volume
- 139
- Issue
- 3
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC12912264
- OpenAlex
- W7128019313
- Cited by
- 2
- References
- 87
- Citations by year
- 2026: 1 · 2025: 1
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- 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
- National Institutes of Health (R01 HL127711, R01 AR072697)
- American Heart Association
- University of Pittsburgh
- 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
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 ›
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