Coordination of Focal Adhesion Nanoarchitecture and Dynamics in Mechanosensing for Cardiomyoblast Differentiation

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Focal adhesions (FAs) are force-bearing multiprotein complexes, whose nanoscale organization and signaling essential for cell growth differentiation. However, the specific of FA components to exert spatiotemporal activation proteins force sensing transduction remains unclear. In this study, we unveil intricacies protein nanoarchitecture that its dynamics coordinated by a molecular scaffold protein, BNIP-2, initiate downstream signal cardiomyoblast Within FAs, BNIP-2 regulates nano-organization focal adhesion kinase (FAK), FAK, paxillin, vinculin. Depletion resulted in altered numbers sizes per cell, reduced traction force, decreased sensitivity mechanosensing. At level, loss disrupted FAK-paxillin axis, where FAK inhibition reproduces effects impairing phosphorylation both paxillin. Mechanistically, preferentially binds constitutively active acts as mediate interactions between paxillin We have validated BNIP-2's role axis human embryonic stem cells (hESC). Furthermore, showed depletion changes signature gene targets at cardiac progenitor stage summary, intricate interplay dynamics, governed is crucial biochemical driving

Language: Английский

Multi-level transcriptomic analysis ofLMNA-related dilated cardiomyopathy identifies disease-driving processes

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 13, 2024

Abstract LMNA- related dilated cardiomyopathy ( LMNA -DCM) is one of the most severe forms DCM. The incomplete understanding molecular disease mechanisms results in lacking treatment options, leading to high mortality amongst patients. Here, using an inducible, cardiomyocyte-specific lamin A/C depletion mouse model, we conducted a comprehensive transcriptomic study, combining both bulk and single nucleus RNA sequencing, spanning -DCM progression, identify potential drivers. Our refined analysis pipeline identified 496 genes already misregulated early disease. expression these was largely driven by specific cardiomyocyte sub-populations involved biological processes mediating cellular response DNA damage, cytosolic pattern recognition, innate immunity. Indeed, damage hearts significantly increased correlated with reduced A levels. Activation recognition cardiomyocytes independent cGAS, which rarely expressed cardiomyocytes, but likely occurred downstream other sensors such as IFI16. Altered gene cardiac fibroblasts immune cell infiltration further contributed tissue-wide changes expression. predicted significant alterations cell-cell communication between fibroblasts, cells, mediated through extracellular matrix (ECM) hearts. Taken together, our work suggests model nuclear leads activation responses, pathway, signaling pathways that activate inflammation, recruitment, transcriptional collectively drive pathogenesis.

Language: Английский