Editing Cilium (section)

==Clinical significance==
{{Main|Ciliopathy}}
Ciliary defects can lead to a number of human diseases.<ref name="Reiter 533–547"/><ref>{{Cite journal|last1=Braun|first1=Daniela A.|last2=Hildebrandt|first2=Friedhelm|date=2017-03-01|title=Ciliopathies|journal=Cold Spring Harbor Perspectives in Biology|volume=9|issue=3|pages=a028191|doi=10.1101/cshperspect.a028191|issn=1943-0264|pmc=5334254|pmid=27793968}}</ref> Defects in cilia adversely affect many critical signaling pathways essential to embryonic development and to adult physiology, and thus offer a plausible hypothesis for the often [[pleiotropic|multi-symptom]] nature of diverse ciliopathies.<ref name="badano2006"/><ref name="Reiter 533–547" /> Known ciliopathies include [[primary ciliary dyskinesia]], [[Bardet–Biedl syndrome]], [[polycystic kidney disease|polycystic kidney]] and [[polycystic liver disease|liver disease]], [[nephronophthisis]], [[Alström syndrome]], [[Meckel–Gruber syndrome]], [[Sensenbrenner syndrome]] and some forms of [[retinopathy|retinal degeneration]].<ref name="badano2006"/><ref name=Adams2008/> Genetic mutations compromising the proper functioning of cilia, [[ciliopathy|ciliopathies]], can cause chronic disorders such as [[primary ciliary dyskinesia]] (PCD), [[nephronophthisis]], and [[Senior–Løken syndrome]]. In addition, a defect of the primary cilium in the [[Nephron#Renal tubule|renal tubule]] 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.<ref name="badano2006"/>  Defects in cilia cells are linked to obesity and often pronounced in type 2 diabetes. Several studies already showed impaired glucose tolerance and reduction in the insulin secretion in the ciliopathy models. Moreover, the number and length of cilia was decreased in the [[type 2 diabetes]] models.<ref>{{cite journal| doi=10.1038/ncomms6308| title=Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents| year=2014| last1=Gerdes| first1=Jantje M.| last2=Christou-Savina| first2=Sonia| last3=Xiong| first3=Yan| last4=Moede| first4=Tilo| last5=Moruzzi| first5=Noah| last6=Karlsson-Edlund| first6=Patrick| last7=Leibiger| first7=Barbara| last8=Leibiger| first8=Ingo B.| last9=Östenson| first9=Claes-Göran| last10=Beales| first10=Philip L.| last11=Berggren| first11=Per-Olof| journal=Nature Communications| volume=5| page=5308| pmid=25374274| bibcode=2014NatCo...5.5308G| s2cid=41645398| doi-access=free}}</ref>

[[Epithelial sodium channels]] (ENaCs) that are expressed along the length of cilia regulate [[Periciliary liquid layer|periciliary fluid]] level. Mutations that decrease the activity of ENaCs result in multisystem [[pseudohypoaldosteronism]], that is associated with fertility problems.<ref name="2012-Enuka" /> In [[cystic fibrosis]] that results from mutations in the chloride channel [[Cystic fibrosis transmembrane conductance regulator|CFTR]], ENaC activity is enhanced leading to a severe reduction of the fluid level that causes complications and infections in the respiratory airways.<ref name="2016-Hanukoglu" />

Since the flagellum of human sperm has the same internal structure of a cilium, ciliary dysfunction can also be responsible for male infertility.<ref name="pmid16850538">{{cite journal | vauthors = Ichioka K, Kohei N, Okubo K, Nishiyama H, Terai A | title = Obstructive azoospermia associated with chronic sinopulmonary infection and situs inversus totalis | journal = Urology | volume = 68 | issue = 1 | pages = 204.e5–7 | date = July 2006 | pmid = 16850538 | doi = 10.1016/j.urology.2006.01.072 }}</ref>

There is an association of primary ciliary dyskinesia with left-right anatomic abnormalities such as [[situs inversus]] (a combination of findings is known as [[Kartagener syndrome]]), and [[situs ambiguus]] (also known as ''Heterotaxy syndrome'').<ref name="Worsley">{{cite journal |last1=Worsley |first1=Calum |last2=Weerakkody |first2=Yuranga |title=Heterotaxy syndrome |url=https://radiopaedia.org/articles/heterotaxy-syndrome?lang=gb |website=Radiopaedia.org |access-date=10 June 2022 |doi=10.53347/rID-7420 |date=1 November 2009|doi-access=free }}</ref> These left-right anatomic abnormalities can also result in [[congenital heart disease]].<ref name="pmid17515466">{{cite journal | vauthors = Kennedy MP, Omran H, Leigh MW, Dell S, Morgan L, Molina PL, Robinson BV, Minnix SL, Olbrich H, Severin T, Ahrens P, Lange L, Morillas HN, Noone PG, Zariwala MA, Knowles MR | title = Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia | journal = Circulation | volume = 115 | issue = 22 | pages = 2814–21 | date = June 2007 | pmid = 17515466 | doi = 10.1161/CIRCULATIONAHA.106.649038 | doi-access = free }}</ref> It has been shown that proper cilial function is responsible for the normal left-right asymmetry in mammals.<ref name="pmid12888012">{{cite journal | vauthors = McGrath J, Brueckner M | title = Cilia are at the heart of vertebrate left-right asymmetry | journal = Current Opinion in Genetics & Development | volume = 13 | issue = 4 | pages = 385–92 | date = August 2003 | pmid = 12888012 | doi = 10.1016/S0959-437X(03)00091-1 }}</ref>

The diverse outcomes caused by ciliary dysfunction may result from alleles of different strengths that compromise ciliary functions in different ways or to different extents. Many ciliopathies are inherited in a Mendelian manner, but specific genetic interactions between distinct functional ciliary complexes, such as transition zone and BBS complexes, can alter the phenotypic manifestations of recessive ciliopathies.<ref>{{Cite journal|last1=Leitch|first1=Carmen C.|last2=Zaghloul|first2=Norann A.|last3=Davis|first3=Erica E.|last4=Stoetzel|first4=Corinne|last5=Diaz-Font|first5=Anna|last6=Rix|first6=Suzanne|last7=Alfadhel|first7=Majid|last8=Al-Fadhel|first8=Majid|last9=Lewis|first9=Richard Alan|last10=Eyaid|first10=Wafaa|last11=Banin|first11=Eyal|date=April 2008|title=Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/18327255|journal=Nature Genetics|volume=40|issue=4|pages=443–448|doi=10.1038/ng.97|issn=1546-1718|pmid=18327255|s2cid=5282929}}</ref><ref>{{Cite journal|last1=Yee|first1=Laura E.|last2=Garcia-Gonzalo|first2=Francesc R.|last3=Bowie|first3=Rachel V.|last4=Li|first4=Chunmei|last5=Kennedy|first5=Julie K.|last6=Ashrafi|first6=Kaveh|last7=Blacque|first7=Oliver E.|last8=Leroux|first8=Michel R.|last9=Reiter|first9=Jeremy F.|date=November 2015|title=Conserved Genetic Interactions between Ciliopathy Complexes Cooperatively Support Ciliogenesis and Ciliary Signaling|journal=PLOS Genetics|volume=11|issue=11|pages=e1005627|doi=10.1371/journal.pgen.1005627|issn=1553-7404|pmc=4635004|pmid=26540106 |doi-access=free }}</ref> Some mutations in transition zone proteins can cause specific serious ciliopathies.<ref name="Cavalier-Smith">{{cite journal |last1=Cavalier-Smith |first1=T |title=Ciliary transition zone evolution and the root of the eukaryote tree: implications for opisthokont origin and classification of kingdoms Protozoa, Plantae, and Fungi. |journal=Protoplasma |date=May 2022 |volume=259 |issue=3 |pages=487–593 |doi=10.1007/s00709-021-01665-7 |pmid=34940909 |pmc=9010356 |bibcode=2022Prpls.259..487C }}</ref>

===Extracellular changes===
Reduction of cilia function can also result from infection. Research into [[biofilm]]s has shown that bacteria can alter cilia. A biofilm is a community of bacteria of either the same or multiple species of bacteria. The cluster of cells secretes different factors which form an extracellular matrix. Cilia in the respiratory system is known to move mucus and pathogens out of the airways. It has been found that patients with biofilm positive infections have impaired cilia function. The impairment may present as decreased motion or reduction in the number of cilia. Though these changes result from an external source, they still effect the pathogenicity of the bacteria, progression of infection, and how it is treated.<ref>{{cite journal | vauthors = Fastenberg JH, Hsueh WD, Mustafa A, Akbar NA, Abuzeid WM | title = Biofilms in chronic rhinosinusitis: Pathophysiology and therapeutic strategies | journal = World Journal of Otorhinolaryngology – Head and Neck Surgery | volume = 2 | issue = 4 | pages = 219–29 | date = December 2016 | pmid = 29204570 | pmc = 5698538 | doi = 10.1016/j.wjorl.2016.03.002 }}</ref>

The transportation of the [[oocyte|immature egg cell]], and the embryo to the [[uterus]] for [[Implantation (human embryo)|implantation]] depends on the combination of regulated smooth muscle contractions, and ciliary beating. Dysfunction in this transportation can result in an [[ectopic pregnancy]] where the embryo is implanted (usually) in the [[fallopian tube]] before reaching its proper destination of the uterus. Many factors can affect this stage including infection and menstrual cycle hormones. Smoking (causing inflammation), and infection can reduce the numbers of cilia, and the ciliary beat can be affected by hormonal changes.<ref name="Panelli">{{cite journal |last1=Panelli |first1=DM |last2=Phillips |first2=CH |last3=Brady |first3=PC |title=Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review. |journal=Fertility Research and Practice |date=2015 |volume=1 |pages=15 |doi=10.1186/s40738-015-0008-z |pmid=28620520|pmc=5424401 |doi-access=free }}</ref><ref>{{cite journal | vauthors = Horne AW, Critchley HO | title = Mechanisms of disease: the endocrinology of ectopic pregnancy | journal = Expert Reviews in Molecular Medicine | volume = 14 | pages = e7 | date = March 2012 | pmid = 22380790 | doi = 10.1017/erm.2011.2 | s2cid = 10039212 }}</ref>

=== Primary cilia in pancreatic cells ===
The pancreas is a mixture of highly differentiated exocrine and endocrine cells. Primary cilia are present in exocrine cells, which are centroacinar duct cells.<ref>{{cite journal|vauthors=Cano DA, Murcia NS, Pazour GJ, Hebrok M|year=2004|title=''orpk'' mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization|journal=Development|volume=131|issue=14|pages=3457–3467|pmid=15226261|doi=10.1242/dev.01189|doi-access=free}}</ref><ref name="Hegyi"/> Endocrine tissue is composed of different hormone-secreting cells. Insulin-secreting beta cells and glucagon-secreting alpha cells are highly ciliated.<ref>{{cite journal|vauthors=Zhang Q, Davenport JR, Croyle MJ, Haycraft CJ, Yoder BK|year=2005|title=Disruption of IFT results in both exocrine and endocrine abnormalities in the pancreas of Tg737(orpk) mutant mice|journal=Laboratory Investigation|volume=85|issue=1|pages=45–64|doi=10.1038/labinvest.3700207|doi-access=free|pmid=15580285}}</ref><ref>{{cite journal|vauthors=Yamamoto M, Kataoka K|year=1986|title=Electron microscopic observation of the primary cilia in the pancreatic islets|journal=Archivum Histologicum Japonicum|volume=49|issue=4|pages=449–457|doi-access=free|doi=10.1679/aohc.49.449|pmid=3545133}}</ref>