Search results for "Cilium"

Cilium induction triggers differentiation of glioma stem cells.

2020

Glioblastoma multiforme (GBM) possesses glioma stem cells (GSCs) that promote self-renewal, tumor propagation, and relapse. Understanding the mechanisms of GSCs self-renewal can offer targeted therapeutic interventions. However, insufficient knowledge of GSCs' fundamental biology is a significant bottleneck hindering these efforts. Here, we show that patient-derived GSCs recruit elevated levels of proteins that ensure the temporal cilium disassembly, leading to suppressed ciliogenesis. Depleting the cilia disassembly complex components is sufficient to induce ciliogenesis in a subset of GSCs via relocating platelet-derived growth factor receptor-alpha (PDGFR-α) to a newly induced cilium. Im…

Light-dependent CK2-mediated phosphorylation of centrins regulates complex formation with visual G-protein.

2008

AbstractCentrins are Ca2+-binding EF-hand proteins. All four known centrin isoforms are expressed in the ciliary apparatus of photoreceptor cells. Cen1p and Cen2p bind to the visual G-protein transducin in a strictly Ca2+-dependent way, which is thought to regulate light driven movements of transducin between photoreceptor cell compartments. These relatively slow motile processes represent a novel paradigm in light adaptation of photoreceptor cells.Here we validated specific phosphorylation as a novel regulator of centrins in photoreceptors. Centrins were differentially phosphorylated during photoreceptor dark adaptation. Inhibitor treatments revealed protein kinase CK2 as the major protein…

IFT46 Expression in the Nasal Mucosa of Primary Ciliary Dyskinesia Patients: Preliminary Study

2021

Este artículo se encuentra disponible en la siguiente URL: https://journals.sagepub.com/doi/pdf/10.1177/2152656721989288 Background: Primary ciliary dyskinesia (PCD) is characterised by an imbalance in mucociliary clearance leading to chronic respiratory infections. Cilia length is considered to be a contributing factor in cilia movement. Recently, IFT46 protein has been related to cilia length. Therefore, this work aims to study IFT46 expression in a PCD patients cohort and analyse its relationship with cilia length and function, as it was not previously described. Materials and methods: The expression of one intraflagellar transport (IFT46) and two regulating ciliary architecture (FOXJ1 a…

2020

X-chromosomal retinitis pigmentosa (RP) frequently is caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. We evaluated the potential of PTC124 (Ataluren, TranslamaTM) treatment to promote ribosomal read-through of premature termination codons (PTC) in RPGR. Expression constructs in HEK293T cells showed that the efficacy of read-through reagents is higher for UGA than UAA PTCs. We identified the novel hemizygous nonsense mutation c.1154T > A, p.Leu385* (NM_000328.3) causing a UAA PTC in RPGR and generated patient-derived fibroblasts. Immunocytochemistry of serum-starved control fibroblasts showed the RPGR protein in a dot-like expression pattern along the primary…

Primary ciliary dyskinesia in adults with bronchiectasis: Data from the Embarc registry

2018

Introduction: Primary ciliary dyskinesia (PCD) is an inherited cause of bronchiectasis where defects in motile cilia result in failure to clear mucus. Individuals have life-long productive cough and recurrent infections Methods: The embarc registry is a prospective pan-European observational study of adults with bronchiectasis. Data entered into the registry between March 2015 and Jan 2018 was assessed. Disease severity in PCD was compared to two age and gender matched cohorts, the first consisting of individuals with immune deficiency and a second with idiopathic disease. Results: 287/11204 individuals (2.6%) were reported to have PCD. 65% were female, reflecting the female predominance in…

Primary ciliary dyskinesia assessment by means of optical flow analysis of phase-contrast microscopy images

2014

Primary ciliary dyskinesia implies cilia with defective or total absence of motility, which may result in sinusitis, chronic bronchitis, bronchiectasis and male infertility. Diagnosis can be difficult and is based on an abnormal ciliary beat frequency (CBF) and beat pattern. In this paper, we present a method to determine CBF of isolated cells through the analysis of phase-contrast microscopy images, estimating cilia motion by means of an optical flow algorithm. After having analyzed 28 image sequences (14 with a normal beat pattern and 14 with a dyskinetic pattern), the normal group presented a CBF of 5.2 +/- 1.6 Hz, while the dyskinetic patients presented a 1.9 +/- 0.9 Hz CBF. The cutoff …

LSC Abstract – Oxidative stress in nasal epithelial cells from patients with primary ciliary dyskinesia

2016

Background: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive inheritance disorder characterized by dysfunction of respiratory cilia and impaired mucociliary clearance, leading to respiratory problems appearing in childhood, decreased fertility and situs inversus in 50% of the cases. The deficient ciliary movement causes stasis of secretions in the airways leading to recurrent airway infection and chronic inflammation. Rationale and aims: Chronic inflammation has been associated to oxidative stress (OS). Moreover, evidence of increased OS in the airways of stable children with PCD has been shown (Zihlif, N. et al . Pediatr Pulmonol 2006; 41:509-14.). Therefore, we hypothesize t…

OFD1mutations in males: phenotypic spectrum and ciliary basal body docking impairment

2012

The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and Cilia to Regulate Ciliogenesis and Ciliary Protein Traffic

2021

ABSTRACTELMODs are a family of three mammalian paralogs that display GTPase activating protein (GAP) activity towards a uniquely broad array of ADP-ribosylation factor (ARF) family GTPases that includes ARF-like (ARL) proteins. ELMODs are ubiquitously expressed in mammalian tissues, highly conserved across eukaryotes, and ancient in origin, being present in the last eukaryotic common ancestor. We described functions of ELMOD2 in immortalized mouse embryonic fibroblasts (MEFs) in the regulation of cell division, microtubules, ciliogenesis, and mitochondrial fusion. Here, using similar strategies with the paralogs ELMOD1 and ELMOD3, we identify novel functions and locations of these cell regu…