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Biochemical Analysis of the Polycystin-1 Complexity Generated by Proteolytic Cleavage at the G Protein-Coupled Receptor Proteolysis Site
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
Rebecca Walker, Hangxue Xu, Qiong Huang, Feng Qian
The primary cilium is an essential cellular organelle whose signaling function within a number of pathways has important connotations for polycystic kidney disease.88 Defective cilia signaling, or mutations in proteins that localize to, or signal through, the cilium result in ciliopathies—a collection of diseases associated with cilia defects.89 Cilia are thought to be involved in maintaining tubular diameter via several pathways, and therefore, as in ADPKD, many ciliopathies include cystic development of the renal architecture.28,90 Despite the ciliary membrane being continuous with the plasma membrane, the cilium is in fact separated from the cell body, being gated at the base by structures associated with the basal body. Proteins that reside in the ciliary membrane or cilioplasm must be transported into the cilium by the intraflagellar transport system.91,92
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Genetics: CED is an autosomal recessive disorder. Four genes have been currently associated with the disease: IFT122, which causes CED1; WDR35 (IFT121), which causes CED2; IFT43 causes CED3; WDR19, which encodes IFT144 and causes CED4. IFT122 is a component of the intraflagellar transport complex A and is involved in retrograde ciliary transport and in the assembly and maintenance of cilia and flagella. WDR35 is a WD40 domain-containing protein and is also implicated in intraflagellar transport. IFT144 and IFT43 are also members of the intraflagellar transport complex.
Intraflagellar transport proteins are involved in thrombocyte filopodia formation and secretion
Published in Platelets, 2018
Uvaraj Radhakrishnan, Abdullah Alsrhani, Hemalatha Sundaramoorthi, Gauri Khandekar, Meghana Kashyap, Jannon L Fuchs, Brian D Perkins, Yoshihiro Omori, Pudur Jagadeeswaran
Intraflagellar transport (IFT) proteins are present mainly in cells that have either a primary cilium or motile cilia. These functionally conserved proteins are critical in the genesis and maintenance of cilia [1–3]. Different, but overlapping sets of IFT proteins compose two IFT complexes: Complex A is mainly for retrograde transport of substances back from the tip of the cilium, and Complex B is for anterograde transport from the base of the cilium to the tip [4,5]. The motor proteins kinesin and dynein move IFT particles with their cargo along microtubules in the anterograde and retrograde direction, respectively. The primary cilium is present in most vertebrate cell types and plays diverse roles in sensory transduction and other types of signaling [6,7]. Defects in IFT proteins can result in short or absent cilia, signaling abnormalities, and associated ciliopathy symptoms in humans and other mammals [8]. In zebrafish, IFT knockdowns and mutations also lead to phenotypic symptoms of defective cilia signaling [9–12].
Renal ciliopathies: promising drug targets and prospects for clinical trials
Published in Expert Opinion on Therapeutic Targets, 2023
Laura Devlin, Praveen Dhondurao Sudhindar, John A. Sayer
During quiescent stages of the cell cycle (G0) the primary cilium is formed, which can also be mimicked by serum starvation in vitro. Upon initiation of ciliogenesis, the mature centriole, a cylindrical 9-fold triplet microtubule structure (150–200 nm diameter, 400–450 nm length) with distal and subdistal appendages, forms the basal body (BB) of the primary cilium [2–4]. The BB anchors to the plasma membrane via distal appendage proteins (DAPs) that project radially from the BB, marking the transition zone region [5,6]. The core BB extends to form the 9-fold doublet microtubule-based axoneme, lacking a central axonemal pair (9+0), rendering it immotile. The primary cilium itself is encased in a ciliary membrane contiguous with the plasma membrane. A discrete ciliary compartment is formed using the transition zone (TZ) of the cilium which cross-links the ciliary membrane with the proximal axonemal microtubules, utilizing Y-links and ciliary necklace proteins and works with DAPs, septin ring barrier, nucleoporins, and other ciliary protein complexes to regulate selective targeting, sorting and localization of molecular cargo [7–10]. Protein complexes integral to ciliary function include the BBSome, MKS complex, NPHP complex, Inversin, and CEP290 complexes [6,11–13]. Intraflagellar transport (IFT) is used to transport protein cargo within the ciliary compartment and is also required for formation of the central axoneme and numerous ciliary signaling pathways [1]. Anterograde movement (up) and retrograde movement (down) is exchanged at the ciliary tip and at other points along the ciliary axoneme [1,14]. Upon entry into the cell cycle, due to the requirement of the mature centriole within the centrosome, the cilium is disassembled and resorbed [15].