Track topics on Twitter Track topics that are important to you
Mutations in the lamin A/C gene (LMNA) cause cardiomyopathy and also disrupt nuclear positioning in fibroblasts. LMNA mutations causing cardiomyopathy elevate ERK1/2 activity in the heart, and inhibition of the ERK1/2 kinase activity ameliorates pathology, but the downstream effectors remain largely unknown. We now show that cardiomyocytes from mice with an Lmna mutation and elevated cardiac ERK1/2 activity have altered nuclear positioning. In fibroblasts, ERK1/2 activation negatively regulated nuclear movement by phosphorylating S498 of FHOD1. Expression of an unphosphorylatable FHOD1 variant rescued the nuclear movement defect in fibroblasts expressing a cardiomyopathy-causing lamin A mutant. In hearts of mice with LMNA mutation-induced cardiomyopathy, ERK1/2 mediated phosphorylation of FHOD3, an isoform highly expressed in cardiac tissue. Phosphorylation of FHOD1 and FHOD3 inhibited their actin bundling activity. These results show that phosphorylation of FHOD proteins by ERK1/2 is a critical switch for nuclear positioning and may play a role in the pathogenesis of cardiomyopathy caused by LMNA mutations.
This article was published in the following journal.
Name: Developmental cell
Matrix metalloproteinases (MMPs) play a pivotal role in tissue remodeling by degrading the extracellular matrix (ECM) components. This mechanism is implicated in a variety of physiological and patholo...
The salvianolate lyophilized injection (SLI) has been widely used for the treatment of acute cerebral infarction; however, the molecular mechanism of how it strengthens blood brain barrier (BBB) funct...
Neuronal excitotoxicity caused by over activation of N -Methyl-D-Aspartate (NMDA) receptors is an important risk factor for the retinal ganglion cells (RGCs) death in glaucoma. D-serine played a role ...
We have previously found that connexin43 is phosphorylated by extracellular-signal-regulated kinase (ERK)1/2 in rats of cerebral ischemia. Here, we investigated the potential roles of microRNA (miR)-3...
Valosin containing protein (VCP), also named p97, is an essential hexameric AAA+ ATPase with diverse functions in the ubiquitin system. Here we demonstrate that VCP is critical in controlling signals ...
The purpose of this study is to investigate the influence of difference positioning on extension and efficacy of brachial plexus anesthesia at 20 minutes by using the axillary plexus block...
Levodopa-induced dyskinesia severely limits the use of levodopa in Parkinson's disease and constitutes a debilitating complication of dopaminergic treatment in late stage. Among several ne...
Knowing the dramatic increase in thrombin generation during sepsis, our research hypothesis is that AMPK-induced ACC phosphorylation in platelets is increased and that this might modulate ...
Fetuin-A has been identified as a novel physiological regulator of insulin action in vitro, in intact cells and in vivo in animals. Previous research has shown that circulating levels of f...
Fragile X Syndrome (FXS) is caused by loss of FMR1 expression on the X chromosome that leads to increased mRNA translation, which results in hyperactivation of ERK (extracellular signal-re...
A nuclear co-repressor protein that shows specificity for RETINOIC ACID RECEPTORS and THYROID HORMONE RECEPTORS. The dissociation of this co-repressor from nuclear receptors is generally ligand-dependent, but can also occur by way of its phosphorylation by members of the MAP KINASE SIGNALING SYSTEM. The protein contains two nuclear receptor interaction domains and four repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 1.
Non-visual system arrestins that negatively regulate G-PROTEIN-COUPLED RECEPTORS (GPCRs) and may also function independently of GPCR signaling. They bind and recruit many different signaling factors, including MITOGEN-ACTIVATED PROTEIN KINASES; SRC-FAMILY-KINASES; and FILAMIN to GPCRs and may recognize different phosphorylation states of the receptors to determine the specificity of the cellular response to signaling.
A specific complex of WNT SIGNALING PATHWAY proteins that mediates the phosphorylation-dependent destruction of cytosolic BETA-CATENIN. The complex is disrupted by cell surface binding of WNT PROTEINS, which allows beta-catenin levels to rise to the point where they migrate to the CELL NUCLEUS and activate transcription.
A lattice of fibrils which covers the entire inner surface of the nuclear envelope and interlinks nuclear pores (NUCLEAR PORE).
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Cardiology is a specialty of internal medicine. Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...