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 ciliopothies.[1]
| Ciliogenesis | |
|---|---|
| Details | |
| Identifiers | |
| Latin | Ciliogenesis |
| TH | H1.00.01.1.01033 |
| Anatomical terminology | |
Cilia Assembly edit
4Primary 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]
Ciliopathies edit
Ciliary defects can lead to a broad range of human diseases known as ciliopathies that are caused by mutations in ciliary proteins. Some common ciliopathies include primary ciliary dyskinesia, hydrocephalus, polycystic liver and kidney disease, and some forms of retinal degeneration. Some research has shown that mutations in ciliary proteins can lead to other developmental and adult phenotypes such as nephronophthisis, Bardet–Biedl syndrome, Alström syndrome, and Meckel–Gruber syndrome.[5]
Regulation edit
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 differ from cell to cell. The processes controlling ciliary formation, degradation, and length must all be regulated in some way to ensure that each cell is able to perform its necessary tasks.
Formation and removal edit
As the cell containing the cilium goes through the cell cycle, ciliogenesis must be regulated. Cilia usually form during the G1 of the cell cycle and disassemble during mitosis. It is not known why the cilia assemble and then disassemble, but it is believed that the presence of cilia may interfere with mitosis and, therefore, are removed before mitosis occurs.[6]
Cells that have recently divided and are in the G0 stage of the cell cycle do not have cilia. During G1, the mother centriole attaches at the cell cortex and forms the cilium. During S-phase, the mother centrioles and daughter centrioles (new centrioles) duplicate and new daughter centrioles are formed. Before mitosis can occur in most cells, the cilium is resorbed back into the cell. After the original cell divides into its two new cells, the cilia reform within the cells after the new cells enter G1.[1]
Length edit
Each type of cell has a specific optimal length for its cilia which therefore need to 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] The regulation of ciliary length is very important because it affects how the cell is able to use its cilia to move fluid over its surface or conduct cellular signaling. Different ciliopathies can be caused by defects in ciliary length. For instance, proteins that have been shown to cause Meckel–Gruber syndrome affect ciliary length control.[7] However, the mechanisms that affect ciliary length control are not understood very well. Until they are, it will be difficult to determine how defects in ciliary length may related to ciliopathic diseases and syndromes.
References edit
- ^ a b c d e f Ishikawa, H.; Marshall, W. (2011). "Ciliogenesis: building the cell's antenna". Molecular Cell Biology. 12 (4): 222–234. doi:10.1038/nrm3085. PMID 21427764. S2CID 33628277.
- ^ a b c d Patel, Maulin M.; Tsiokas, Leonidas (2021). "Insights into the Regulation of Ciliary Disassembly". Cells. 10 (11): 2977. doi:10.3390/cells10112977. ISSN 2073-4409.
- ^ rupress.org https://rupress.org/jcb/article/15/2/363/16155/CENTRIOLES-AND-THE-FORMATION-OF-RUDIMENTARY-CILIA. Retrieved 2024-04-25.
{{cite web}}: Missing or empty|title=(help) - ^ a b c d Avidor-Reiss, Tomer; Leroux, Michel R. (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.
- ^ Badano, J.; Mitsuma, N.; Beales, P.; Katsanis, N. (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.
- ^ Parker, J. D. K.; et al. (2010). "Centrioles are freed from cilia by severing prior to mitosis". Cytoskeleton. 67 (7): 425–430. doi:10.1002/cm.20454. PMC 2897710. PMID 20506243.
- ^ Tammachote, R. et al. Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3. Hum. Mol. Genet. 18, 3311–3323 (2009).