scholarly journals Transcriptomic Coupling of PKP2 With Inflammatory and Immune Pathways Endogenous to Adult Cardiac Myocytes

2021 ◽  
Vol 11 ◽  
Author(s):  
Marta Pérez-Hernández ◽  
Grecia M. Marrón-Liñares ◽  
Florencia Schlamp ◽  
Adriana Heguy ◽  
Chantal J. M. van Opbergen ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Transcript Abundance ◽  
Cell Contact ◽  
Plakophilin 2 ◽  
Intracellular Signals ◽  
Adult Cardiac Myocytes ◽  
Inflammatory Immune Response ◽  
Cell Cell

Plakophilin-2 (PKP2) is classically defined as a component of the desmosome. Besides its role in cell–cell adhesion, PKP2 can modulate transcription through intracellular signals initiated at the site of cell–cell contact. Mutations in PKP2 associate with arrhythmogenic right ventricular cardiomyopathy (ARVC). Recent data demonstrate that inflammation plays a key role in disease progression; other results show an abundance of anti-heart antibodies in patients with confirmed diagnosis of ARVC. Here, we test the hypothesis that, in adult cardiac myocytes, PKP2 transcript abundance is endogenously linked to the abundance of transcripts participating in the inflammatory/immune response. Cardiac-specific, tamoxifen (TAM)-activated PKP2-knockout mice (PKP2cKO) were crossed with a RiboTag line to allow characterization of the ribosome-resident transcriptome of cardiomyocytes after PKP2 knockdown. Data were combined with informatics analysis of human cardiac transcriptome using GTEx. Separately, the presence of non-myocyte cells at the time of analysis was assessed by imaging methods. We identified a large number of transcripts upregulated consequent to PKP2 deficiency in myocytes, inversely correlated with PKP2 abundance in human transcriptomes, and part of functional pathways associated with inflammatory/immune responses. Our data support the concept that PKP2 is transcriptionally linked, in cardiac myocytes, to genes coding for host-response molecules even in the absence of exogenous triggers. Targeted anti-inflammatory therapy may be effective in ARVC.

Cell-cell contact between adult rat cardiac myocytes regulates Kv1.5 and Kv4.2 K+channel mRNA expression

1998 ◽  
Vol 275 (6) ◽  
pp. C1473-C1480 ◽  
Author(s):  
Kenneth M. Hershman ◽  
Edwin S. Levitan
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Cardiac Myocytes ◽  
Cell Density ◽  
Cardiac Myocyte ◽  
Live Cells ◽  
K Channel ◽  
Cell Contact ◽  
Adult Cardiac Myocytes ◽  
Cell Cell

Regulation of voltage-gated K+channel genes represents an important mechanism for modulating cardiac excitability. Here we demonstrate that expression of two K+channel mRNAs is reciprocally controlled by cell-cell interactions between adult cardiac myocytes. It is shown that culturing acutely dissociated rat ventricular myocytes for 3 h results in a dramatic downregulation of Kv1.5 mRNA and a modest upregulation of Kv4.2 mRNA. These effects are specific, because similar changes are not detected with other channel mRNAs. Increasing myocyte density promotes maintenance of Kv1.5 gene expression, whereas Kv4.2 mRNA expression was found to be inversely proportional to cell density. Conditioned culture medium did not mimic the effects of high cell density. However, paraformaldehyde-fixed myocytes were comparable to live cells in their ability to influence K+channel message levels. Thus the reciprocal effects of cell density on the expression of Kv1.5 and Kv4.2 genes are mediated by direct contact between adult cardiac myocytes. These findings reveal for the first time that cardiac myocyte gene expression is influenced by signaling induced by cell-cell contact.

scholarly journals Desmoplakin assembly dynamics in four dimensions

2005 ◽  
Vol 171 (6) ◽  
pp. 1045-1059 ◽  
Author(s):  
Lisa M. Godsel ◽  
Sherry N. Hsieh ◽  
Evangeline V. Amargo ◽  
Amanda E. Bass ◽  
Lauren T. Pascoe-McGillicuddy ◽  
...  
Keyword(s):  
Intermediate Filament ◽  
Particle Trajectory ◽  
De Novo ◽  
Time Lapse ◽  
Cell Contact ◽  
Four Dimensions ◽  
Tissue Integrity ◽  
Plakophilin 2 ◽  
Time Lapse Imaging ◽  
Cell Cell

The intermediate filament (IF)–binding protein desmoplakin (DP) is essential for desmosome function and tissue integrity, but its role in junction assembly is poorly understood. Using time-lapse imaging, we show that cell–cell contact triggers three temporally overlapping phases of DP-GFP dynamics: (1) the de novo appearance of punctate fluorescence at new contact zones after as little as 3 min; (2) the coalescence of DP and the armadillo protein plakophilin 2 into discrete cytoplasmic particles after as little as 15 min; and (3) the cytochalasin-sensitive translocation of cytoplasmic particles to maturing borders, with kinetics ranging from 0.002 to 0.04 μm/s. DP mutants that abrogate or enhance association with IFs exhibit delayed incorporation into junctions, altering particle trajectory or increasing particle pause times, respectively. Our data are consistent with the idea that DP assembles into nascent junctions from both diffusible and particulate pools in a temporally overlapping series of events triggered by cell–cell contact and regulated by actin and DP–IF interactions.

scholarly journals Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation

2014 ◽  
Vol 25 (23) ◽  
pp. 3749-3764 ◽  
Author(s):  
Viktor Todorovic´ ◽  
Jennifer L. Koetsier ◽  
Lisa M. Godsel ◽  
Kathleen J. Green
Keyword(s):  
Initial Phase ◽  
Adherens Junction ◽  
Cell Contact ◽  
Functional Association ◽  
Plakophilin 2 ◽  
Plakophilin 3 ◽  
E Cadherin ◽  
Cell Cell

The pathways driving desmosome and adherens junction assembly are temporally and spatially coordinated, but how they are functionally coupled is poorly understood. Here we show that the Armadillo protein plakophilin 3 (Pkp3) mediates both desmosome assembly and E-cadherin maturation through Rap1 GTPase, thus functioning in a manner distinct from the closely related plakophilin 2 (Pkp2). Whereas Pkp2 and Pkp3 share the ability to mediate the initial phase of desmoplakin (DP) accumulation at sites of cell–cell contact, they play distinct roles in later steps: Pkp3 is required for assembly of a cytoplasmic population of DP-enriched junction precursors, whereas Pkp2 is required for transfer of the precursors to the membrane. Moreover, Pkp3 forms a complex with Rap1 GTPase, promoting its activation and facilitating desmosome assembly. We show further that Pkp3 deficiency causes disruption of an E-cadherin/Rap1 complex required for adherens junction sealing. These findings reveal Pkp3 as a coordinator of desmosome and adherens junction assembly and maturation through its functional association with Rap1.

Characterization of N-cadherin-containing cell-cell contacts of the liver

2006 ◽  
Vol 44 (01) ◽  
Author(s):  
BK Straub ◽  
J Boda-Heggemann ◽  
UF Pape ◽  
C Grund ◽  
E Specht-Delius ◽  
...  
Keyword(s):  
Cell Contacts ◽  
Cell Cell

Tumor Necrosis Factor-α Provokes a Hypertrophic Growth Response in Adult Cardiac Myocytes

Circulation ◽  
1997 ◽  
Vol 95 (5) ◽  
pp. 1247-1252 ◽  
Author(s):  
Tomoyuki Yokoyama ◽  
Masayuki Nakano ◽  
John L. Bednarczyk ◽  
Bradley W. McIntyre ◽  
Mark Entman ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cardiac Myocytes ◽  
Tumor Necrosis ◽  
Growth Response ◽  
Tumor Necrosis Factor Α ◽  
Hypertrophic Growth ◽  
Adult Cardiac Myocytes ◽  
Factor Α ◽  
Necrosis Factor
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