Centrin 2 is required for mouse olfactory ciliary trafficking and development of ependymal cilia planar polarity.
Centrins are ancient calmodulin-related Ca(2+)-binding proteins associated with basal bodies. In lower eukaryotes, Centrin2 (CETN2) is required for basal body replication and positioning, although its function in mammals is undefined. We generated a germline CETN2 knock-out (KO) mouse presenting with syndromic ciliopathy including dysosmia and hydrocephalus. Absence of CETN2 leads to olfactory cilia loss, impaired ciliary trafficking of olfactory signaling proteins, adenylate cyclase III (ACIII), and cyclic nucleotide-gated (CNG) channel, as well as disrupted basal body apical migration in postnatal olfactory sensory neurons (OSNs). In mutant OSNs, cilia base-anchoring of intraflagellar transport components IFT88, the kinesin-II subunit KIF3A, and cytoplasmic dynein 2 appeared compromised. Although the densities of mutant ependymal and respiratory cilia were largely normal, the planar polarity of mutant ependymal cilia was disrupted, resulting in uncoordinated flow of CSF. Transgenic expression of GFP-CETN2 rescued the Cetn2-deficiency phenotype. These results indicate that mammalian basal body replication and ciliogenesis occur independently of CETN2; however, mouse CETN2 regulates protein trafficking of olfactory cilia and participates in specifying planar polarity of ependymal cilia.
Departments of Ophthalmology, and Neurobiology and Anatomy, University of Utah Health Science Center, Salt Lake City, Utah 84132, and Departments of Physiology and Biology, University of Utah, Salt Lake City, Utah 84112.
Guoxin
G
Ying
Prachee
P
Avasthi
Mavis
M
Irwin
Cecilia D
CD
Gerstner
Jeanne M
JM
Frederick
Mary T
MT
Lucero
Wolfgang
W
Baehr
D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity / Q000235:genetics; D002923:Cilia / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D004848:Epithelium / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D006849:Hydrocephalus / Q000150:complications / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009812:Odorants; D000857:Olfaction Disorders / Q000150:complications / Q000235:genetics / Q000473:pathology; D009830:Olfactory Bulb / Q000473:pathology*; D000439:Pentanols / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics*
D002135:Calcium-Binding Proteins; C424436:Cetn2 protein, mouse; D000439:Pentanols; D049452:Green Fluorescent Proteins; C005716:amyl acetate
centrin 2 knock-out; ciliary maintenance; ciliary trafficking; ependymal cilia; olfactory cilia; planar cell polarity