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Bardet−Biedl Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Located on the surface of different types of cells, cilia are the tiny hair-like structures (either motile or immotile) that utilize an architectural element known as basal body to anchor to a cell. Possessing central microtubule pair necessary for ciliary mobility, motile cilia propel fluid (e.g., mucus) through the local environment and assist in cell motility. Immotile (primary) cilia have unique 9 + 0 structure with nine microtubule triplets arranged in a circle with an outer membrane, and participate in cell signaling, left-right asymmetry, tissue formation, and homeostasis. In the eyes, rod and cone photoreceptor cells of the retina are known to utilize their immotile cilia for light-perceiving function [5].
The liver, gallbladder and pancreas
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Dina G. Tiniakos, Alastair D. Burt
The intrahepatic biliary tree originates from the surrounding developing liver and this process involves complex control of cell proliferation, migration, and programmed cell death. Failure of this process during intrauterine life can result in a spectrum of ‘ductal plate malformations’ causing failure of normal bile flow in infancy and later life, e.g. mutation of the gene Jagged-1 is associated with the failure of differentiation or survival of bile ducts resulting in atresia of ducts seen as part of Alagille syndrome (Figure 11.1). Mutations in PKD genes encoding polycystins, proteins found in the primary cilia of bile duct cells (and renal tubule cells), result in a common hereditary disease with cysts in multiple organs including the liver.
Recording Ion Channels in Cilia Membranes
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
Leo C.T. Ng, Amitabha Mukhopadhyay, Thuy N. Vien, Paul G. DeCaen
Primary cilia are visualized from live primary cells and tissues of transgenic mice that stably express cilia-specific fluorophores.38 Previously, we stably expressed the ARL13B transgene conjugated to enhanced green fluorescent protein (Arl13B-EGFPtg) in the genome of a founder C57BL/6 mouse. ARL13B (ADP-ribosylation factor-like protein 13B) is enriched but is not exclusively trafficked to motile and primary cilia. Importantly, Arl13B-EGFPtg mice do not have a distinct behavioral or anatomical phenotype from C57BL/6 mice.38,45 Furthermore, overexpression of the transgene does not alter the size or number of motile and primary cilia based on histological analyses of the lung, kidney, and eye. Heterozygous or homozygous expression of the transgene is sufficient for cilia visualization in situ or from cultured cells with green fluorescence protein (GFP) excitation under a standard widefield or confocal microscope. To facilitate cilia patch clamp experiments, we have successfully isolated ciliated hippocampal neurons, ependymal cells, RPE, MEF, and primary IMCD cells using tissue specific dissociation protocols to create primary cultures of each cell type.52–54 When grown on a monolayer, the apical side with their projecting cilia invariably faces the top of the culture dish, which is easily accessible to a patch electrode (see Section 3.3.4).
Retinal dystrophy as part of TTC21B-associated ciliopathy
Published in Ophthalmic Genetics, 2021
Tamar Ben-Yosef, Nurit Asia Batsir, Tahleel Ali Nasser, Miriam Ehrenberg
Ciliopathies are a group of inherited diseases caused by mutations in genes associated with the structure and function of primary cilia. Primary cilia function as signaling hubs that sense environmental cues and are pivotal for organ development and function, and for tissue homeostasis. By their nature, cilia defects are usually pleiotropic, affecting more than one system (1). Organs that are commonly affected in ciliopathies are the central nervous system, kidney, liver, pancreas, skeletal system, inner ear, and retina. In the retina, photoreceptor outer segments are highly modified primary sensory cilia. The proximal end of the outer segment is linked to the cell body (i.e. the inner segment) via a connecting cilium which is structurally homologous to the transition zone of primary cilia (2). Consequently, retinal pathogenesis is a common finding in ciliopathies. Some examples of the better-known ciliopathies associated with retinal dystrophies (RD) are Bardet-Biedel Syndrome (3), Usher Syndrome (4), Joubert Syndrome, (5) and Senior-Loken Syndrome (6).
A homozygous POC1B variant causes recessive cone-rod dystrophy
Published in Ophthalmic Genetics, 2021
Ann-Marie C. Peturson, Nicole C. L. Noel, Ian M. MacDonald
Inherited retinal dystrophies are diverse groups of photoreceptor disorders, with many genetic etiologies. Cone dystrophies are characterized by the dysfunction and loss of cone photoreceptors. An initial diagnosis of cone dystrophy can progress to cone-rod dystrophy as rod photoreceptors degenerate. Variants in components of the photoreceptor cilium are common causes of photoreceptor dystrophies. The POC1 centriolar protein B (POC1B) gene encodes a component of the centrosome and basal body of the photoreceptor cilium (Figure 1) (1). The centrosome, which is comprised of two centrioles surrounded by a protein mass, forms the primary cilia basal body. POC1B has been reported to play essential roles in centriole duplication and length, centriole integrity, cell proliferation, primary ciliogenesis, and retinal integrity (2–5). Pathogenic variants in POC1B have been associated with autosomal recessive cone dystrophy, cone-rod dystrophy, and syndromic retinal dystrophy (1,5–8). Here, we present a cone-rod dystrophy patient with a homozygous POC1B variant, further expanding the clinical findings for patients with POC1B variants.
PLK4: a link between centriole biogenesis and cancer
Published in Expert Opinion on Therapeutic Targets, 2018
Radhika Radha Maniswami, Seema Prashanth, Archana Venkataramana Karanth, Sindhu Koushik, Hemalatha Govindaraj, Ramesh Mullangi, Sriram Rajagopal, Sooriya Kumar Jegatheesan
Ciliogenesis begins with the nucleation of the mother centriole that functions as a basal body to template primary cilia [84]. PLK4-dependent phosphorylation of PCM1 is necessary for ciliogenesis. PLK4 phosphorylates PCM1 at a conserved S372 position and promotes dimerization/oligomerization. It also stimulates interaction of PCM1 with other centriolar satellite components such as hMsd1/SSX2IP, BBS4, and CEP290 resulting in increased aggregation and localization of centriolar satellites. Integrity of centriolar satellite components is an important prerequisite for ciliogenesis. It has been observed that depletion of PLK4 results in dispersion of centriolar satellites and perturbed ciliogenesis leading to loss of primary cilia [103]. This result in defective signaling since primary cilia coordinates a series of pathways that include Hedgehog, Wnt, PDGFRα, integrin and cell differentiation signaling pathways [104,105].