filamin

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Critical periods are temporally-restricted, early-life windows when sensory experience remodels synaptic connectivity to optimize environmental input. In the Drosophila juvenile brain, critical period experience drives synapse elimination, which is transiently reversible. Within olfactory sensory neuron (OSN) classes synapsing onto single projection neurons extending to brain learning/memory centers, we find glia mediate experience-dependent pruning of OSN synaptic glomeruli downstream of critical period odorant exposure...

BACKGROUND: Filamin A (FLNA) is a member of filamin family and has been found to be critical for the progression of several cancers. However, its biological function in papillary thyroid cancer (PTC) remains largely unexplored. METHODS: Data from The Cancer Genome Atlas (TCGA) databases were utilized to analyze the FLNA expression level and its influence on the clinical implication of patients with PTC. Gene Expression Omnibus (GEO) and quantitative real-time reverse transcriptase PCR (qRT-PCR) was used to verify the expression levels of FLNA in PTC...

Curcumin is a kind of polyphenol substance extracted from the rhizome of Curcuma longa. Because of its good biological activity and pharmacological effects, it has been used in anti-tumor research. The aim of this study was to investigate the anti-cancer mechanism of curcumin on laryngeal squamous cell carcinoma (LSCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to check the expression level of transcription factor E2F1 (E2F1) and filamin A (FLNA) mRNA. E2F1 and FLNA protein and proliferation-associated protein were detected through western blot...

Filamin C (FLNC) is a highly important actin crosslinker and multi-adaptor protein in striated skeletal and cardiac muscle. Mutations have been linked to a range of cardiomyopathy types. Here, we generated induced pluripotent stem cells (iPSC) from a patient with dilated cardiomyopathy (DCM) harboring a new, unique heterozygous FLNC mutation p.R2187P. From this patient-specific iPSC line, a corresponding isogenic control line was created by CRISPR/Cas9 genome editing. Both, the patient-specific and isogenic-control iPSC maintained full pluripotency, genomic integrity, and in vitro differentiation capacity...

In Drosophila, only one cell in a multicellular female germline cyst is specified as an oocyte and a similar process occurs in mammals. The symmetry-breaking cue for oocyte selection is provided by the fusome, a tubular structure connecting all cells in the cyst. The Drosophila spectraplakin Shot localises to the fusome and translates its asymmetry into a polarised microtubule network that is essential for oocyte specification, but how Shot recognises the fusome is unclear. Here, we demonstrate that the actin-binding domain (ABD) of Shot is necessary and sufficient to localise Shot to the fusome and mediates Shot function in oocyte specification together with the microtubule-binding domains...

Forensic pathologists are frequently asked to investigate cases of sudden death (SD), and identifying the cause of death can be of particular importance, especially where it may be necessary to perform family screening among the relatives of the victim. A multidisciplinary approach inclusive of genetic analysis is therefore strongly recommended. According to forensic practice, arrhythmogenic cardiomyopathy (ACM) is a well-known cause of SD. However, cases of SD caused by a left ventricular pattern of ACM diagnosed at autopsy are rarely reported in the literature...

Ameloblastoma (AM) is a prominent benign odontogenic tumor characterized by aggressiveness, likely originating from tooth-generating tissue or the dental follicle (DF). However, proteomic distinctions between AM and DF remain unclear. In the present study, the aim was to identify the distinction between AM and DF in terms of their proteome and to determine the associated hub genes. Shotgun proteomics was used to compare the proteomes of seven fresh-frozen AM tissues and five DF tissues. Differentially expressed proteins (DEPs) were quantified and subsequently analyzed through Gene Ontology-based functional analysis, protein-protein interaction (PPI) analysis and hub gene identification...

BACKGROUND: The exact mechanisms underlying the pathogenesis of myocarditis are not always understood, but there is emerging evidence to suggest that genetic factors may play a significant role. CASE SUMMARY: Herein, we present six cases in which clinical, biochemical, and cardiovascular magnetic resonance data were consistent with myocarditis, and genetic testing subsequently revealed pathogenic filamin C (FLNC) mutations. Three patients presented with ventricular arrhythmias, two with severe biventricular dysfunction, and two suffered sudden cardiac arrest...

Actin-binding filamin C (FLNC) is expressed in cardiomyocytes, where it localizes to Z-discs, sarcolemma, and intercalated discs. Although FLNC truncation variants ( FLNCtv ) are an established cause of arrhythmias and heart failure, changes in biomechanical properties of cardiomyocytes are mostly unknown. Thus, we investigated the mechanical properties of human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) carrying FLNCtv . CRISPR/Cas9 genome-edited homozygous FLNCKO-/- hiPSC-CMs and heterozygous knock-out FLNCKO+/- hiPSC-CMs were analyzed and compared to wild-type FLNC (FLNCWT ) hiPSC-CMs...

Filamin B (FLNB) plays an important role in skeletal development. Mutations in FLNB can lead to skeletal malformation such as an abnormal number of ossification centers, indicating that the skeletal segmentation in the embryonic period may be interfered with. We established a mouse model with the pathogenic point mutation FLNB NM_001081427.1: c.4756G > A (p.Gly1586Arg) using CRISPR-Cas9 technology. Micro-CT, HE staining and whole skeletal preparation were performed to examine the skeletal malformation...

Dipeptidyl peptidase 9 (DPP9) is an intracellular amino-dipeptidase with physiological roles in the immune system, DNA repair and mitochondria homeostasis, while its deregulation is linked to cancer progression and immune-associated defects. Through its rare ability to cleave a peptide bond following the imino-acid proline, DPP9 acts as a molecular switch that regulates key proteins, such as the tumor-suppressor BRCA2. In this review we will discuss key concepts underlying the outcomes of protein processing by DPP9, including substrate turn-over by the N-degron pathway...

Pancreatic cancer (PC) is an immunosuppressive cancer. Immune-based therapies that enhance or recruit antitumor immune cells into the tumor microenvironment (TME) remain promising strategies for PC treatment. Consequently, a deeper understanding of the molecular mechanisms involved in PC immune suppression is critical for developing immune-based therapies to improve survival rates. In this study, weighted gene co-expression network analysis (WGCNA) was used to identify Filamin B (FLNB) correlated with the infiltration of CD8+ T cells and tumor-associated macrophages (TAMs)...

An early diagnosis of Alzheimer's disease is crucial as treatment efficacy is limited to the early stages. However, the current diagnostic methods are limited to mid or later stages of disease development owing to the limitations of clinical examinations and amyloid plaque imaging. Therefore, this study aimed to identify molecular signatures including blood plasma extracellular vesicle biomarker proteins associated with Alzheimer's disease to aid early-stage diagnosis. The hippocampus, cortex, and blood plasma extracellular vesicles of 3- and 6-month-old 5xFAD mice were analyzed using quantitative proteomics...

Dilated cardiomyopathy (DCM) is a common heart muscle disorder of nonischemic etiology associated with heart failure development and the risk of malignant ventricular arrhythmias and sudden cardiac death. A tailored approach to risk stratification and prevention of sudden cardiac death is required in genetic DCM given its variable presentation and phenotypic severity. Currently, advances in cardiogenetics have shed light on disease mechanisms, the complex genetic architecture of DCM, polygenic contributors to disease susceptibility and the role of environmental triggers...

Vaccinia virus (VACV) is a large DNA virus that encodes scores of proteins that modulate the host immune response. VACV protein C4 is one such immunomodulator known to inhibit the activation of both the NF-κB signaling cascade and the DNA-PK-mediated DNA sensing pathway. Here, we show that the N-terminal region of C4, which neither inhibits NF-κB nor mediates interaction with DNA-PK, still contributes to virus virulence. Furthermore, this domain interacts directly and with high affinity to the C-terminal domain of filamin B (FLNB)...

Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, PSA's screening utility is diminished, resulting in many unnecessary biopsies. To address this issue, we previously identified a cleaved fragment of Filamin A (FLNA) protein (as measured with IP-MRM mass spectrometry assessment as a prognostic biomarker for stratifying BPH from prostate cancer and subsequently evaluated its expanded utility in Caucasian (CA) and African American (AA) men...

Filamin C-related disorders include myopathies and cardiomyopathies linked to variants in the FLNC gene. Filamin C belongs to a family of actin-binding proteins involved in sarcomere stability. This study investigates the pathogenic impact of the FLNC c.3557C > T (p.Ala1186Val) pathogenic variant associated with an early-onset cytoplasmic body myopathy and cardiomyopathy in three unrelated patients. We performed clinical imaging and myopathologic and genetic characterization of three patients with an early-onset myopathy and cardiomyopathy...

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research suggests that they may be regulated by both distinct and shared pathways. Specifically, recent studies have indicated that both CIP and CIL utilize mechanotransduction pathways, a process that involves cells sensing and responding to mechanical forces...

Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a unidirectional fashion. How such mechanical cues affect CTL evasion of perforin-mediated autolysis remains unclear. Here we show that activated CTLs use their softness to evade perforin-mediated autolysis, which, however, is shared by T leukemic cells to evade CTL killing. Downregulation of filamin A is identified to induce softness via ZAP70-mediated YAP Y357 phosphorylation and activation...