The cilium is a membrane-bound organelle found on most types of eukaryotic cell. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projection that extends from the surface of the much larger cell body. Eukaryotic flagella found on sperm cells and many protozoans have a similar structure to motile cilia that enables swimming through liquids; they are longer than cilia and have a different undulating motion.
A basal body is a protein structure found at the base of a eukaryotic undulipodium. The basal body was named by Theodor Wilhelm Engelmann in 1880. It is formed from a centriole and several additional protein structures, and is, essentially, a modified centriole. The basal body serves as a nucleation site for the growth of the axoneme microtubules. Centrioles, from which basal bodies are derived, act as anchoring sites for proteins that in turn anchor microtubules, and are known as the microtubule organizing center (MTOC). These microtubules provide structure and facilitate movement of vesicles and organelles within many eukaryotic cells.
In molecular biology, an axoneme, also called an axial filament, is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axoneme serves as the "skeleton" of these organelles, both giving support to the structure and, in some cases, the ability to bend. Though distinctions of function and length may be made between cilia and flagella, the internal structure of the axoneme is common to both.
Intraflagellar transport (IFT) is a bidirectional motility along axoneme microtubules that is essential for the formation (ciliogenesis) and maintenance of most eukaryotic cilia and flagella. It is thought to be required to build all cilia that assemble within a membrane projection from the cell surface. Plasmodium falciparum cilia and the sperm flagella of Drosophila are examples of cilia that assemble in the cytoplasm and do not require IFT. The process of IFT involves movement of large protein complexes called IFT particles or trains from the cell body to the ciliary tip and followed by their return to the cell body. The outward or anterograde movement is powered by kinesin-2 while the inward or retrograde movement is powered by cytoplasmic dynein 2/1b. The IFT particles are composed of about 20 proteins organized in two subcomplexes called complex A and B.
The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper cell differentiation. Different parts of the embryo have different concentrations of hedgehog signaling proteins. The pathway also has roles in the adult. Diseases associated with the malfunction of this pathway include cancer.
Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the natural teratogen cyclopamine. It also is the target of vismodegib, the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA).
Polycystin 1 (PC1) is a protein that in humans is encoded by the PKD1 gene. Mutations of PKD1 are associated with most cases of autosomal dominant polycystic kidney disease, a severe hereditary disorder of the kidneys characterised by the development of renal cysts and severe kidney dysfunction.
X-linked retinitis pigmentosa GTPase regulator is a GTPase-binding protein that in humans is encoded by the RPGR gene. The gene is located on the X-chromosome and is commonly associated with X-linked retinitis pigmentosa (XLRP). In photoreceptor cells, RPGR is localized in the connecting cilium which connects the protein-synthesizing inner segment to the photosensitive outer segment and is involved in the modulation of cargo trafficked between the two segments.
Planar cell polarity (PCP) is the protein-mediated signaling that coordinates the orientation of cells in a layer of epithelial tissue. In vertebrates, examples of mature PCP oriented tissue are the stereo-cilia bundles in the inner ear, motile cilia of the epithelium, and cell motility in epidermal wound healing. Additionally, PCP is known to be crucial to major developmental time points including coordinating convergent extension during gastrulation and coordinating cell behavior for neural tube closure. Cells orient themselves and their neighbors by establishing asymmetric expression of PCP components on opposing cell members within cells to establish and maintain the directionality of the cells. Some of these PCP components are transmembrane proteins which can proliferate the orientation signal to the surrounding cells.
Conorenal syndrome, is a collection of medical conditions that seem to have a common genetic cause.
A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function. Primary cilia are important in guiding the process of development, so abnormal ciliary function while an embryo is developing can lead to a set of malformations that can occur regardless of the particular genetic problem. The similarity of the clinical features of these developmental disorders means that they form a recognizable cluster of syndromes, loosely attributed to abnormal ciliary function and hence called ciliopathies. Regardless of the actual genetic cause, it is clustering of a set of characteristic physiological features which define whether a syndrome is a ciliopathy.
RPGRIP1L is a human gene.
Mechanosensation is the transduction of mechanical stimuli into neural signals. Mechanosensation provides the basis for the senses of light touch, hearing, proprioception, and pain. Mechanoreceptors found in the skin, called cutaneous mechanoreceptors, are responsible for the sense of touch. Tiny cells in the inner ear, called hair cells, are responsible for hearing and balance. States of neuropathic pain, such as hyperalgesia and allodynia, are also directly related to mechanosensation. A wide array of elements are involved in the process of mechanosensation, many of which are still not fully understood.
72 kDa inositol polyphosphate 5-phosphatase, also known as phosphatidylinositol-4,5-bisphosphate 5-phosphatase or Pharbin, is an enzyme that in humans is encoded by the INPP5E gene.
Xaa-Pro aminopeptidase 3, also known as aminopeptidase P3, is an enzyme that in humans is encoded by the XPNPEP3 gene. XPNPEP3 localizes to mitochondria in renal cells and to kidney tubules in a cell type-specific pattern. Mutations in XPNPEP3 gene have been identified as a cause of a nephronophthisis-like disease.
Sensenbrenner syndrome is a rare multisystem disease first described by Judith A. Sensenbrenner in 1975. It is inherited in an autosomal recessive fashion, and a number of genes appear to be responsible. Three genes responsible have been identified: intraflagellar transport (IFT)122 (WDR10), IFT43—a subunit of the IFT complex A machinery of primary cilia, and WDR35
Ciliogenesis is defined as the building of the cell's antenna or extracellular fluid mediation mechanism. It includes the assembly and disassembly of the cilia during the cell cycle. Cilia are important appendages of cells and are involved in numerous activities such as cell signaling, processing developmental signals, and directing the flow of fluids such as mucus over and around cells. Due to the importance of these cell processes, defects in ciliogenesis can lead to numerous human diseases related to non-functioning cilia known as ciliopathies.
Pleasantine Mill is a cell biologist and group leader at the MRC Human Genetics Unit at the University of Edinburgh. She won the 2018 British Society for Cell Biology Women in Cell Biology Early Career Medal.
RVxP motif is a protein motif involved in localizing proteins into cilia.
Gaia Pigino is the Associate Head of the Structural Biology Research Center and Research Group Leader of the Pigino Group at the Human Technopole in Milan, Italy.
