Jump to content

Cilium: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Isaghoul (talk | contribs)
24 edits
→Cilium-related disease: added citation
Line 78: Line 78:
== Structure, assembly, maintenance, and function ==
== Structure, assembly, maintenance, and function ==
[[File:Eukaryotic cilium diagram en.svg|thumb|300px|Eukaryotic motile cilium]]
[[File:Eukaryotic cilium diagram en.svg|thumb|300px|Eukaryotic motile cilium]]
Inside cilia and [[flagella]] is a [[microtubule]]-based [[cytoskeleton]] called the [[axoneme]]. The axoneme of primary cilia typically has a ring of nine outer microtubule doublets (called a 9+0 axoneme), and the axoneme of a motile cilium has two central microtubule singlets in addition to the nine outer doublets (called a 9+2 axoneme). The axonemal cytoskeleton acts as a scaffolding for various [[protein]] complexes and provides binding sites for [[molecular machine|molecular motor]] proteins such as [[kinesin|kinesin II]], that help carry proteins up and down the microtubules.<ref name="HHMIB2005"/><ref>{{cite journal|last=rosenbaum|first=JL|author2=Witman G|title=Intraflagellar transport|journal=Nature Reviews Molecular Cell Biology|volume=3|pages=813–25|pmid=12415299|doi=10.1038/nrm952|issue=11|date=November 2002}}</ref><ref>{{cite journal|last=Scholey|first=JM|title=Intraflagellar transport motors in cilia: Moving along the cell's antenna.|journal=Journal of Cell Biology|year=2008|volume=180|pages=23–29|pmid=18180368|doi=10.1083/jcb.200709133|pmc=2213603}}</ref>
Inside cilia and [[flagella]] is a [[microtubule]]-based [[cytoskeleton]] called the [[axoneme]]. The axoneme of primary cilia typically has a ring of nine outer microtubule doublets (called a 9+0 axoneme), and the axoneme of a motile cilium has two central microtubule singlets in addition to the nine outer doublets (called a 9+2 axoneme). The axonemal cytoskeleton acts as a scaffolding for various [[protein]] complexes and provides binding sites for [[molecular machine|molecular motor]] proteins such as [[kinesin|kinesin II]], that help carry proteins up and down the microtubules.<ref name="HHMIB2005"/><ref>{{cite journal|last=rosenbaum|first=JL|author2=Witman G|title=Intraflagellar transport|journal=Nature Reviews Molecular Cell Biology|volume=3|pages=813–25|pmid=12415299|doi=10.1038/nrm952|issue=11|date=November 2002}}</ref><ref>{{cite journal|last=Scholey|first=JM|title=Intraflagellar transport motors in cilia: Moving along the cell's antenna.|journal=Journal of Cell Biology|year=2008|volume=180|pages=23–29|pmid=18180368|doi=10.1083/jcb.200709133|pmc=2213603}}</ref> On the outside of cilia is a membrane that is like the plasma membrane, but compositionally distinct due to a blocking ring ("necklace") around the base<ref>{{cite web|url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910237/|title = The Ciliary Membrane|year=2010|first = Rajat |last = Rohatgi1|first = William|last = Snell2}}</ref>, and distinct also in its population of receptors and other integral proteins.


The [[dynein]] in the axoneme forms bridges between neighbouring microtubule doublets. When ATP activates the motor domain of dynein, it attempts to walk along the adjoining microtubule doublet. This would force the adjacent doublets to slide over one another if not for the presence of [[Nexin]] between the microtubule doublets. And thus the force generated by dyenin is instead converted into a bending motion.<ref>{{Cite web|url = https://www.ncbi.nlm.nih.gov/books/NBK26888/|title = Molecular Biology of the Cell|date = |accessdate = |website = |publisher = |last = Alberts|first = Bruce}}</ref>
The [[dynein]] in the axoneme forms bridges between neighbouring microtubule doublets. When ATP activates the motor domain of dynein, it attempts to walk along the adjoining microtubule doublet. This would force the adjacent doublets to slide over one another if not for the presence of [[Nexin]] between the microtubule doublets. And thus the force generated by dyenin is instead converted into a bending motion.<ref>{{Cite web|url = https://www.ncbi.nlm.nih.gov/books/NBK26888/|title = Molecular Biology of the Cell|date = |accessdate = |website = |publisher = |last = Alberts|first = Bruce}}</ref>

Revision as of 21:48, 31 October 2017

This article is about organelles. For fine hairs on insect wings, see Cilium (entomology).
Not to be confused with Psyllium.
Cilium
SEM micrograph of the cilia projecting from respiratory epithelium in the lungs
Details
Identifiers
LatinCilium
MeSHD002923
THH1.00.01.1.01014
FMA67181
Anatomical terminology

A cilium (Latin for eyelash;[1] the plural is cilia) is an organelle found in eukaryotic cells. Cilia are slender protuberances that project from the much larger cell body.[2] Cilium can measure up to 20 µm and have a diameter around 0.25 µm. [3]

There are two types of cilia: motile cilia and nonmotile, or primary cilia, which typically serve as sensory organelles. In eukaryotes, motile cilia and flagella together make up a group of organelles known as undulipodia.[4] Eukaryotic cilia are structurally identical to eukaryotic flagella, although distinctions are sometimes made according to function and/or length.[5] Biologists have various ideas about how the various flagella may have evolved.

Types and distribution

Cilia can be divided into primary and motile forms.[6]

Primary/Immotile cilia

In animals, primary cilia are found on nearly every cell.[2]

In comparison to motile cilia, non-motile (or primary) cilia usually occur one per cell; nearly all mammalian cells have a single non-motile primary cilium. In addition, examples of specialized primary cilia can be found in human sensory organs such as the eye and the nose:

Although the primary cilium was discovered in 1898, it was largely ignored for a century. Only recently has great progress been made in understanding the function of the primary cilium. Until the 1990s, the prevailing view of the primary cilium was that it was merely a vestigial organelle without important function.[2] Recent findings regarding its physiological roles in chemical sensation, signal transduction, and control of cell growth, have led scientists to acknowledge its importance in cell function, with the discovery of its role in diseases not previously recognized to involve the dysgenesis and dysfunction of cilia, such as polycystic kidney disease,[8] congenital heart disease,[9] and an emerging group of genetic ciliopathies.[10] The primary cilium is now known to play an important role in the function of many human organs.[2] The current scientific understanding of primary cilia views them as "sensory cellular antennae that coordinate a large number of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation.".[11]

Illustration depicting motile cilia.

Motile cilia

Larger eukaryotes, such as mammals, have motile cilia as well. Motile cilia are usually present on a cell's surface in large numbers and beat in coordinated waves.[12]

The functioning of motile cilia is strongly dependent on the maintenance of optimal levels of fluid bathing the cilia. Epithelial sodium channels ENaC that are specifically expressed along the entire length of cilia apparently serve as sensors that regulate fluid level surrounding the cilia.[13][15]

Ciliates are microscopic organisms that possess motile cilia exclusively and use them for either locomotion or to simply move liquid over their surface.

Structure, assembly, maintenance, and function

Eukaryotic motile cilium

Inside cilia and flagella is a microtubule-based cytoskeleton called the axoneme. The axoneme of primary cilia typically has a ring of nine outer microtubule doublets (called a 9+0 axoneme), and the axoneme of a motile cilium has two central microtubule singlets in addition to the nine outer doublets (called a 9+2 axoneme). The axonemal cytoskeleton acts as a scaffolding for various protein complexes and provides binding sites for molecular motor proteins such as kinesin II, that help carry proteins up and down the microtubules.[2][16][17] On the outside of cilia is a membrane that is like the plasma membrane, but compositionally distinct due to a blocking ring ("necklace") around the base[18], and distinct also in its population of receptors and other integral proteins.

The dynein in the axoneme forms bridges between neighbouring microtubule doublets. When ATP activates the motor domain of dynein, it attempts to walk along the adjoining microtubule doublet. This would force the adjacent doublets to slide over one another if not for the presence of Nexin between the microtubule doublets. And thus the force generated by dyenin is instead converted into a bending motion.[19]

Cilia are formed through the process of ciliogenesis. The building blocks of the cilia such as tubulins and other partially assembled axonemal proteins are added to the ciliary tips which point away from the cell body.[20] In most species bi-directional motility called intraflagellar transport (IFT) plays an essential role in moving these building materials from the cell body to the assembly site.[21] IFT also carries the disassembled material to be recycled from the ciliary tip back to the cell body. By regulating the equilibrium between these two IFT processes, the length of cilia can be maintained dynamically. Disassembly of cilia requires the action of the Aurora A kinase .[22]

Exceptions where IFT is not present include Plasmodium falciparum, which is one of the species of Plasmodium that cause malaria in humans. In this parasite, cilia assemble in the cytoplasm.[23]

At the base of the cilium where it attaches to the cell body is the microtubule organizing center, the basal body. Some basal body proteins as CEP164, ODF2 [24] and CEP170,[25] regulate the formation and the stability of the cilium. A transition zone between the basal body and the axoneme "serves as a docking station for intraflagellar transport and motor proteins."[2]

In effect, the cilium is a nanomachine composed of perhaps over 600 proteins in molecular complexes, many of which also function independently as nanomachines.[11]

Ciliary rootlet

The ciliary rootlet is a cytoskeleton-like structure that originates from the basal body at the proximal end of a cilium. It extends proximally toward the cell nucleus. Rootlets are typically 80-100 nm in diameter and contain cross striae distributed at regular intervals of approximately 55-70 nm. According to the Gene Ontology, the following proteins localize to the ciliary rootlet: amyloid precursor protein, rootletin, kinesins (KIF5B, KIF5C, KLC2, KLC3), and presenilins (PSEN1, PSEN2).[26]

Sensing the extracellular environment

Some primary cilia on epithelial cells in eukaryotes act as cellular antennae, providing chemosensation, thermosensation and mechanosensation of the extracellular environment.[27] These cilia then play a role in mediating specific signalling cues, including soluble factors in the external cell environment, a secretory role in which a soluble protein is released to have an effect downstream of the fluid flow, and mediation of fluid flow if the cilia are motile.[27] Some epithelial cells are ciliated, and they commonly exist as a sheet of polarized cells forming a tube or tubule with cilia projecting into the lumen. This sensory and signalling role puts cilia in a central role for maintaining the local cellular environment and may be why ciliary defects cause such a wide range of human diseases.[28]

Main article: Ciliopathy

Ciliary defects can lead to a number of human diseases. Genetic mutations compromising the proper functioning of cilia, ciliopathies, can cause chronic disorders such as primary ciliary dyskinesia (PCD), nephronophthisis or Senior-Loken syndrome. In addition, a defect of the primary cilium in the renal tube cells can lead to polycystic kidney disease (PKD). In another genetic disorder called Bardet-Biedl syndrome (BBS), the mutant gene products are the components in the basal body and cilia.[10]

Lack of functional cilia in female Fallopian tubes can cause ectopic pregnancy. A fertilized ovum may not reach the uterus if the cilia are unable to move it there. In such a case, the ovum will implant in the Fallopian tubes, causing a tubal pregnancy, the most common form of ectopic pregnancy.[29]

As noted above, epithelial sodium channels ENaC that are expressed along the length of cilia regulate fluid level surrounding the cilia. Mutations that decrease the activity of ENaC result in multisystem pseudohypoaldosteronism, that is associated with fertility problems.[13] In cystic fibrosis that results from mutations in the chloride channel CFTR, ENaC activity is enhanced leading to a severe reduction of the fluid level that causes complications and infections in the respiratory airways.[15]

Since the flagellum of human sperm is actually a modified cilium, ciliary dysfunction can also be responsible for male infertility.[30]

Of interest, there is an association of primary ciliary dyskinesia with left-right anatomic abnormalities such as situs inversus (a combination of findings known as Kartagener's syndrome) and other heterotaxic defects. These left-right anatomic abnormalities can also result in congenital heart disease.[31] It has been shown that proper cilial function is responsible for the normal left-right asymmetry in mammals.[32]

Ciliopathy as an origin for many multi-symptom genetic diseases

Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously related in the medical literature, may be, in fact, highly related in the root cause of the widely varying set of medical symptoms that are clinically visible in the disorder. These have been grouped as an emerging class of diseases called ciliopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary/immotile cilia, organelles which are present in many diverse cellular types throughout the human body. Cilia defects adversely affect numerous critical developmental signaling pathways essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases.[10] Known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome, Sensenbrenner syndrome and some forms of retinal degeneration.[10][27]

See also

References

  1. ^ Mosby’s Medical, Nursing and Allied Health Dictionary, Fourth Edition, Mosby-Year Book Inc., 1994, p. 336
  2. ^ a b c d e f Gardiner, Mary Beth (September 2005). "The Importance of Being Cilia" (PDF). HHMI Bulletin. 18 (2). Howard Hughes Medical Institute. Retrieved 26 July 2008.
  3. ^ "Cilium". biologydictionary.net. Retrieved 8 September 2017.
  4. ^ A Dictionary of Biology , 2004, accessed 2010-04-06.
  5. ^ Haimo LT, Rosenbaum JL (December 1981). "Cilia, flagella, and microtubules". J. Cell Biol. 91 (3 Pt 2): 125s–130s. doi:10.1083/jcb.91.3.125s. PMC 2112827. PMID 6459327.
  6. ^ Karen Field Murray (1 June 2009). Fibrocystic Diseases of the Liver. Springer. pp. 47–. ISBN 978-1-60327-523-1. Retrieved 25 November 2010.
  7. ^ Wolfrum, U., & Schmitt, A. (2000). Rhodopsin transport in the membrane of the connecting cilium of mammalian photoreceptor cells. Cell motility and the cytoskeleton, 46(2), 95-107.
  8. ^ Wagner CA (2008). "News from the cyst: insights into polycystic kidney disease". Journal of Nephrology. 21 (1): 14–6. PMID 18264930.
  9. ^ Brueckner M (June 2007). "Heterotaxia, congenital heart disease, and primary ciliary dyskinesia". Circulation. 115 (22): 2793–5. doi:10.1161/CIRCULATIONAHA.107.699256. PMID 17548739.
  10. ^ a b c d Badano JL, Mitsuma N, Beales PL, Katsanis N (2006). "The ciliopathies: an emerging class of human genetic disorders". Annual Review of Genomics and Human Genetics. 7: 125–48. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803.
  11. ^ a b Satir, Peter; Christensen, Søren T. (2008). "Structure and function of mammalian cilia". Histochemistry and Cell Biology. 129 (6): 687–93. doi:10.1007/s00418-008-0416-9. PMC 2386530. PMID 18365235.
  12. ^ Benjamin Lewin (2007). Cells. Jones & Bartlett Learning. p. 359. ISBN 978-0-7637-3905-8. Retrieved 25 November 2010.
  13. ^ a b c d Enuka Y, Hanukoglu I, Edelheit O, Vaknine H, Hanukoglu A (March 2012). "Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways". Histochemistry and Cell Biology. 137 (3): 339–53. doi:10.1007/s00418-011-0904-1. PMID 22207244.
  14. ^ "Cilia in nature" (PDF). hitech-projects.com. 2007. Retrieved 28 July 2008.
  15. ^ a b Hanukoglu I, Hanukoglu A (January 2016). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases". Gene. 579 (2): 95–132. doi:10.1016/j.gene.2015.12.061. PMC 4756657. PMID 26772908.
  16. ^ rosenbaum, JL; Witman G (November 2002). "Intraflagellar transport". Nature Reviews Molecular Cell Biology. 3 (11): 813–25. doi:10.1038/nrm952. PMID 12415299.
  17. ^ Scholey, JM (2008). "Intraflagellar transport motors in cilia: Moving along the cell's antenna". Journal of Cell Biology. 180: 23–29. doi:10.1083/jcb.200709133. PMC 2213603. PMID 18180368.
  18. ^ Snell2, William (2010). "The Ciliary Membrane".{{cite web}}: CS1 maint: numeric names: authors list (link)
  19. ^ Alberts, Bruce. "Molecular Biology of the Cell".
  20. ^ Johnson, KA; Rosenbaum, JL (1992). "Polarity of flagellar assembly in Chlamydomonas". Journal of Cell Biology. 119 (6): 1605–1611. doi:10.1083/jcb.119.6.1605. PMC 2289744. PMID 1281816.
  21. ^ Hao, L; Thein M; Brust-Mascher I; Civelekoglu-Scholey G; Lu Y; Acar S; Prevo B; Shaham S; Scholey JM (2011). "Intraflagellar transport delivers tubulin isotypes to sensory cilium middle and distal segments". Nature Cell Biology. 13 (7): 790–798. doi:10.1038/ncb2268. PMC 3129367. PMID 21642982.
  22. ^ Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA (June 2007). "HEF1-dependent Aurora A activation induces disassembly of the primary cilium". Cell. 129 (7): 1351–63. doi:10.1016/j.cell.2007.04.035. PMC 2504417. PMID 17604723.
  23. ^ Of cilia and silliness (more on Behe) - The Panda's Thumb Archived 17 October 2007 at the Wayback Machine
  24. ^ Ishikawa H, Kubo A, Tsukita S, Tsukita S (May 2005). "Odf2-deficient mother centrioles lack distal/subdistal appendages and the ability to generate primary cilia". Nature Cell Biology. 7 (5): 517–24. doi:10.1038/ncb1251. PMID 15852003.
  25. ^ "Functional characterisation of the centrosomal protein Cep170".
  26. ^ "Ciliary Rootlet". Gene Ontology. Retrieved 13 June 2012.
  27. ^ a b c Adams, M.; Smith, U. M.; Logan, C. V.; Johnson, C. A. (2008). "Recent advances in the molecular pathology, cell biology and genetics of ciliopathies". Journal of Medical Genetics. 45 (5): 257–267. doi:10.1136/jmg.2007.054999. PMID 18178628.
  28. ^ Singla, Veena; Reiter, Jeremy F. (August 2006). "The primary cilium as the cell's antenna: signaling at a sensory organelle". Science. 313 (5787): 629–633. doi:10.1126/science.1124534. PMID 16888132.
  29. ^ Horne, Andrew W.; Critchley, Hilary O. D. (2 March 2012). "Mechanisms of disease: the endocrinology of ectopic pregnancy". Expert Reviews in Molecular Medicine. 14: e7. doi:10.1017/erm.2011.2. ISSN 1462-3994. PMID 22380790.
  30. ^ Ichioka K, Kohei N, Okubo K, Nishiyama H, Terai A (July 2006). "Obstructive azoospermia associated with chronic sinopulmonary infection and situs inversus totalis". Urology. 68 (1): 204.e5–7. doi:10.1016/j.urology.2006.01.072. PMID 16850538.
  31. ^ Kennedy MP, Omran H, Leigh MW, et al. (June 2007). "Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia". Circulation. 115 (22): 2814–21. doi:10.1161/CIRCULATIONAHA.106.649038. PMID 17515466.
  32. ^ McGrath J, Brueckner M (August 2003). "Cilia are at the heart of vertebrate left-right asymmetry". Current Opinion in Genetics & Development. 13 (4): 385–92. doi:10.1016/S0959-437X(03)00091-1. PMID 12888012.

Retrieved from "https://en.wikipedia.org/w/index.php?title=Cilium&oldid=808100029"