Centrin 2 is required for mouse olfactory ciliary trafficking and development of ependymal cilia planar polarity.
J Neurosci
; 34(18): 6377-88, 2014 Apr 30.
Article
em En
| MEDLINE
| ID: mdl-24790208
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bulbo Olfatório
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Proteínas de Ligação ao Cálcio
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Cílios
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Regulação da Expressão Gênica no Desenvolvimento
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Transporte Proteico
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Epitélio
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2014
Tipo de documento:
Article