Palladin (PALLD) belongs to the PALLD/myopalladin (MYPN)/myotilin family of actin-associated immunoglobulin-containing proteins in the sarcomeric Z-line. PALLD is ubiquitously expressed in several isoforms, and its longest 200 kDa isoform, predominantly expressed in striated muscle, shows high structural homology to MYPN. gene mutations are associated with human cardiomyopathies, whereas the role of PALLD in the heart has remained unknown, partly due to embryonic lethality of PALLD knockout mice. In a yeast two-hybrid screening, CARP/Ankrd1 and FHOD1 were identified as novel interaction partners of PALLD's N-terminal region. To study the role of PALLD in the heart, we generated conditional (cPKO) and inducible (cPKOi) cardiomyocyte-specific PALLD knockout mice. While cPKO mice exhibited no pathological phenotype, ablation of PALLD in adult cPKOi mice caused progressive cardiac dilation and systolic dysfunction, associated with reduced cardiomyocyte contractility, intercalated disc abnormalities, and fibrosis, demonstrating that PALLD is essential for normal cardiac function. Double cPKO and MYPN knockout (MKO) mice exhibited a similar phenotype as MKO mice, suggesting that MYPN does not compensate for the loss of PALLD in cPKO mice. Altered transcript levels of and isoforms were found in myocardial tissue from human dilated and ischemic cardiomyopathy patients, whereas their protein expression levels were unaltered.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069870 | PMC |
| http://dx.doi.org/10.7554/eLife.78629 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Single-Cell Transcriptomics Identifies Selective Lineage-Specific Regulation of Genes in Aortic Smooth Muscle Cells in Mice.
Arterioscler Thromb Vasc Biol
January 2025
Division of Cardiology, Department of Medicine, University of Washington (S.S., S.J., N.S., C.Y.L., L.L., D.A.D.).
Article Synopsis
- The study investigates the differences between smooth muscle cells (SMCs) from two lineages in the proximal thoracic aorta, specifically the second heart field (SHF) and cardiac neural crest.
- Researchers used advanced techniques like single-cell RNA sequencing and chromatin accessibility assays to analyze these cells in male mice, identifying distinct gene expressions in both lineages.
- Findings reveal that SHF-derived SMCs have unique transcriptomic profiles that may influence their functions in thoracic aortic diseases, suggesting lineage-specific roles in vascular health.
The actin-binding protein palladin associates with the respiratory syncytial virus matrix protein.
J Virol
October 2024
Biomedical Research Cluster, Faculty of Science and Technology, University of Canberra, Canberra, Australia.
The respiratory syncytial virus (RSV) matrix (M) protein plays an important role in infection as it can interact with viral components as well as the host cell actin microfilaments. The M-actin interaction may play a role in facilitating the transportation of virion components to the apical surface, where RSV is released. We show that M protein's association with actin is facilitated by palladin, an actin-binding protein.
View Article and Find Full Text PDFGenetics of Cardiac Aging Implicate Organ-Specific Variation.
medRxiv
August 2024
Division of Cardiology, University of California San Francisco, San Francisco, CA, USA.
Heart structure and function change with age, and the notion that the heart may age faster for some individuals than for others has driven interest in estimating cardiac age acceleration. However, current approaches have limited feature richness (heart measurements; radiomics) or capture extraneous data and therefore lack cardiac specificity (deep learning [DL] on unmasked chest MRI). These technical limitations have been a barrier to efforts to understand genetic contributions to age acceleration.
View Article and Find Full Text PDFThe role of PALLD-STAT3 interaction in megakaryocyte differentiation and thrombocytopenia treatment.
Haematologica
November 2024
Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai.
Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, however the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes.
View Article and Find Full Text PDFSingle-cell RNA sequencing and ATAC sequencing identify novel biomarkers for bicuspid aortic valve-associated thoracic aortic aneurysm.
Front Cardiovasc Med
April 2024
School of Medicine, Guangxi University, Nanning, China.
Introduction: Bicuspid aortic valve (BAV) is the most prevalent congenital cardiovascular defect and known to cause thoracic aortic aneurysms (TAAs). To improve our understanding of BAV pathogenesis, we characterized the cellular composition of BAV tissues and identified molecular changes in each cell population.
Methods: Tissue samples from two patients with BAV and two heart transplant donors were analyzed using single-cell RNA sequencing, assay for transposase-accessible chromatin using sequencing, and weighted gene coexpression network analysis for differential gene analysis.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!