Ciliogenesis

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Ciliogenesis
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Identifiers
Latin Ciliogenesis
TH H1.00.01.1.01033
Anatomical terminology
EVOS Imaging depicting a single celled organism with distinctive cilia Paramecia.png
EVOS Imaging depicting a single celled organism with distinctive cilia

Ciliogenesis is defined as the building of the cell's antenna (primary cilia) or extracellular fluid mediation mechanism (motile cilium). [1] 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. [1]

Contents

Assembly

Cilia Structure Cilia Estructura.png
Cilia Structure

Primary cilia are found to be formed when a cell exits the cell cycle. [2] Cilia consist of four main compartments: the basal body at the base, the transition zone, the axenome which is an arrangement of nine doublet microtubules and considered to be the core of the cilium, and the ciliary membrane. [2] Primary cilia contain nine doublet microtubules arranged as a cylinder in their axenome and are denoted as a 9+0 pattern. [2] Motile cilia are denoted as a 9+2 pattern because they contain two extra microtubules in the center of the cylinder that forms the axenome. [2] Due to differences between primary and motile cilia, differences are seen in the formation process.

Ciliogenesis occurs through an ordered set of steps. [3] Basal bodies migrate to the surface of the cell and attach to the cell cortex. Along the way, the basal bodies attach to membrane vesicles that fuse with the plasma membrane of the cell. The alignment of cilia is determined by the positioning and orientation of the basal bodies at this step. Once the alignment is determined, axonemal microtubules extend from the basal body and forming the cilia. [1]

Proteins must be synthesized in the cytoplasm of the cell and cannot be synthesized within cilia. For the cilium to elongate, proteins must be selectively imported from the cytoplasm into the cilium and transported to the tip of the cilium by intraflagellar transport (IFT). Once the cilium is completely formed, it continues to incorporate new tubulin at the tip of the cilia while older tubulin is simultaneously degraded. This requires an active mechanism that maintains ciliary length. Impairments in these mechanisms can affect the motility of the cell and cell signaling between cells. [1]

There are two noted types of ciliogenesis: compartmentalized and cytosolic. [4] Most cells undergo compartmentalized ciliogenesis in which cilia are enveloped by extensions of the plasma membrane for the entirety of development. [4] In cytosolic ciliogenesis, the axenome must interact with proteins in the cytoplasm therefore it is directly exposed to the cytoplasm. [4] In some cells, cytosolic ciliogenesis occurs after compartmentalized ciliogenesis. [4]

Disassembly

Cilia disassembly is much less understood than cilia assembly. From recent discoveries, three distinct types of cilia disassembly have been identified. One variety of cilia disassembly occurs when the length of the cilia is gradually reduced until it is no longer functional. [5] Another category of cilia disassembly is shedding where cilia are severed from the main cell body. [5] An example of this is Chlamydomonas in which a severing enzyme known as katanin separates basal bodies from axenomes. [5]

In some organisms, a third method of cilia disassembly has been seen in which the entire axenome is internalized and then later disintegrated. [2]

Cilia presence is seen to be inversely related to the progression of the cell cycle which can be seen by assembly occurring during cellular quiescence and disassembly occurring when the cell cycle is stimulated. [2]

Regulation

Different cells use their cilia for different purposes, such as sensory signaling or the movement of fluid. For this reason, when cilia form and how long they are can differ from cell to cell. The processes controlling ciliary formation, degradation, and length must be regulated to ensure that each cell is able to perform its necessary tasks.

Each type of cell has an optimal length for its cilia which must be regulated to ensure optimal function of the cell. Some of the same processes that are used to control the formation and removal of cilia (such as IFT) are thought to be used in the regulation of cilia length. [1] Cilia length also differs depending on where a cell is in the cell cycle. [2]

Three categories of molecular events that potentially regulate cilia disassembly include activation of AurA kinase and deacetylation of microtubules, depolymerization of microtubules, and ciliary membrane remodeling. [2]

Cilia regulation is grossly understudied; however, dysregulation of ciliogenesis is linked to several diseases.

Ciliopathies

Ciliary defects can lead to a broad range of human diseases known as ciliopathies that are caused by mutations in ciliary proteins. Because of how widespread cilia are, defects can cause ciliopathies in many different regions of the body. [4]

Cilia also play a role in cell signaling and the cell cycle therefore defects to them can have a serious impact on the cell’s ability to function. [4]

Some common ciliopathies include primary ciliary dyskinesia, hydrocephalus, polycystic liver and kidney disease, some forms of retinal degeneration, nephronophthisis, Bardet–Biedl syndrome, Alström syndrome, and Meckel–Gruber syndrome. [6]

Related Research Articles

<span class="mw-page-title-main">Centriole</span> Organelle in eukaryotic cells that produces cilia and organizes the mitotic spindle

In cell biology a centriole is a cylindrical organelle composed mainly of a protein called tubulin. Centrioles are found in most eukaryotic cells, but are not present in conifers (Pinophyta), flowering plants (angiosperms) and most fungi, and are only present in the male gametes of charophytes, bryophytes, seedless vascular plants, cycads, and Ginkgo. A bound pair of centrioles, surrounded by a highly ordered mass of dense material, called the pericentriolar material (PCM), makes up a structure called a centrosome.

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

<span class="mw-page-title-main">Flagellum</span> Cellular appendage functioning as locomotive or sensory organelle

A flagellum is a hairlike appendage that protrudes from certain plant and animal sperm cells, from fungal spores (zoospores), and from a wide range of microorganisms to provide motility. Many protists with flagella are known as flagellates.

<span class="mw-page-title-main">Cilium</span> Organelle found on eukaryotic cells

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.

<span class="mw-page-title-main">Cytoskeleton</span> Network of filamentous proteins that forms the internal framework of cells

The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components: microfilaments, intermediate filaments, and microtubules, and these are all capable of rapid growth or disassembly depending on the cell's requirements.

<span class="mw-page-title-main">Cytokinesis</span> Part of the cell division process

Cytokinesis is the part of the cell division process and part of mitosis during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meiosis. During cytokinesis the spindle apparatus partitions and transports duplicated chromatids into the cytoplasm of the separating daughter cells. It thereby ensures that chromosome number and complement are maintained from one generation to the next and that, except in special cases, the daughter cells will be functional copies of the parent cell. After the completion of the telophase and cytokinesis, each daughter cell enters the interphase of the cell cycle.

The microtubule-organizing center (MTOC) is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spindle apparatus, which separate the chromosomes during cell division. The MTOC is a major site of microtubule nucleation and can be visualized in cells by immunohistochemical detection of γ-tubulin. The morphological characteristics of MTOCs vary between the different phyla and kingdoms. In animals, the two most important types of MTOCs are 1) the basal bodies associated with cilia and flagella and 2) the centrosome associated with spindle formation.

<span class="mw-page-title-main">Basal body</span> Protein structure found at the base of cilium or flagellum).

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.

<span class="mw-page-title-main">Axoneme</span> Protein structure forming the core of cilia and flagellae

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.

<span class="mw-page-title-main">Stathmin</span> Protein in Eukaryotes

Stathmin, also known as metablastin and oncoprotein 18 is a protein that in humans is encoded by the STMN1 gene.

<span class="mw-page-title-main">Intraflagellar transport</span> Cellular process

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.

<span class="mw-page-title-main">CEP290</span> Protein-coding gene in the species Homo sapiens

Centrosomal protein of 290 kDa is a protein that in humans is encoded by the CEP290 gene. CEP290 is located on the Q arm of chromosome 12.

<span class="mw-page-title-main">Ciliopathy</span> Genetic disease resulting in abnormal formation or function of cilia

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.

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.

<span class="mw-page-title-main">Amoeboid movement</span> Mode of locomotion in eukaryotic cells

Amoeboid movement is the most typical mode of locomotion in adherent eukaryotic cells. It is a crawling-like type of movement accomplished by protrusion of cytoplasm of the cell involving the formation of pseudopodia ("false-feet") and posterior uropods. One or more pseudopodia may be produced at a time depending on the organism, but all amoeboid movement is characterized by the movement of organisms with an amorphous form that possess no set motility structures.

A BBSome is a protein complex that operates in primary cilia biogenesis, homeostasis, and intraflagellar transport (IFT). The BBSome recognizes cargo proteins and signaling molecules like G-protein coupled receptors (GPCRs) on the ciliary membrane and helps transport them to and from the primary cilia. Primary cilia are nonmotile microtubule projections that function like antennae and are found in many types of cells. They receive various environmental signals to aid the cell in survival. They can detect photons by concentrating rhodopsin, a light receptor that converts photons into chemical signals, or odorants by concentrating olfactory receptors on the primary cilia surface. Primary cilia are also meaningful in cell development and signaling. They do not contain any way to make proteins within the primary cilia, so the BBSome aids in transporting essential proteins to, from, and within the cilia. Examples of cargo proteins that the BBSome is responsible for ferrying include smoothened, polycystic-1 (PC1), and several G-Protein coupled receptors (GPCRs) like somatostatin receptors (Sstr3), melanin-concentrating hormone receptor 1 (Mchr1), and neuropeptide Y2 receptor.

Cytosolic ciliogenesis, otherwise cytoplasmic ciliogenesis, is a type of ciliogenesis where the cilium axoneme is formed in the cytoplasm or becomes exposed to the cytoplasm.

Compartmentalized ciliogenesis is the most common type of ciliogenesis where the cilium axoneme is formed separated from the cytoplasm by the ciliary membrane and a ciliary gate known as the transition zone.

RVxP motif is a protein motif involved in localizing proteins into cilia.

<span class="mw-page-title-main">Jeremy Reiter</span> American developmental geneticist

Jeremy Reiter is an American developmental geneticist who is the chair of the Department of Biochemistry and Biophysics at the University of California, San Francisco (UCSF). He is holder of the Albert Bowers Endowed Chair. His research focuses on the cilium, particularly in understanding its role in cell signaling and its involvement in human diseases such as cancer, congenital disorders and obesity.

References

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  2. 1 2 3 4 5 6 7 8 Patel MM, Tsiokas L (November 2021). "Insights into the Regulation of Ciliary Disassembly". Cells. 10 (11): 2977. doi: 10.3390/cells10112977 . PMC   8616418 . PMID   34831200.
  3. Sorokin S (November 1962). "Centrioles and the formation of rudimentary cilia by fibroblasts and smooth muscle cells". The Journal of Cell Biology. 15 (2): 363–77. doi:10.1083/jcb.15.2.363. PMC   2106144 . PMID   13978319.
  4. 1 2 3 4 5 6 Avidor-Reiss T, Leroux MR (December 2015). "Shared and Distinct Mechanisms of Compartmentalized and Cytosolic Ciliogenesis". Current Biology. 25 (23): R1143–R1150. Bibcode:2015CBio...25R1143A. doi:10.1016/j.cub.2015.11.001. PMC   5857621 . PMID   26654377.
  5. 1 2 3 Sánchez I, Dynlacht BD (June 2016). "Cilium assembly and disassembly". Nature Cell Biology. 18 (7): 711–717. doi:10.1038/ncb3370. PMC   5079433 . PMID   27350441.
  6. Badano JL, Mitsuma N, Beales PL, Katsanis N (September 2006). "The ciliopathies: an emerging class of human genetic disorders". Annual Review of Genomics and Human Genetics. 7 (1): 125–148. doi:10.1146/annurev.genom.7.080505.115610. PMID   16722803.