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XB-ART-51433
Development December 1, 2015; 142 (23): 4068-79.

The NIMA-like kinase Nek2 is a key switch balancing cilia biogenesis and resorption in the development of left-right asymmetry.

Endicott SJ , Basu B , Khokha M , Brueckner M .


Abstract
Vertebrate left-right (LR) asymmetry originates at a transient left-right organizer (LRO), a ciliated structure where cilia play a crucial role in breaking symmetry. However, much remains unknown about the choreography of cilia biogenesis and resorption at this organ. We recently identified a mutation affecting NEK2, a member of the NIMA-like serine-threonine kinase family, in a patient with congenital heart disease associated with abnormal LR development. Here, we report how Nek2 acts through cilia to influence LR patterning. Both overexpression and knockdown of nek2 in Xenopus result in abnormal LR development and reduction of LRO cilia count and motility, phenotypes that are modified by interaction with the Hippo signaling pathway. nek2 knockdown leads to a centriole defect at the LRO, consistent with the known role of Nek2 in centriole separation. Nek2 overexpression results in premature ciliary resorption in cultured cells dependent on function of the tubulin deacetylase Hdac6. Finally, we provide evidence that the known interaction between Nek2 and Nup98, a nucleoporin that localizes to the ciliary base, is important for regulating cilium resorption. Together, these data show that Nek2 is a switch balancing ciliogenesis and resorption in the development of LR asymmetry.

PubMed ID: 26493400
PMC ID: PMC4712839
Article link: Development
Grant support: [+]
Genes referenced: aurka cep85 dand5 hdac6 kif11 lefty nek2 nin nodal nup98 pifo pitx2 stk24 stk3 wnt11
GO keywords: determination of left/right asymmetry in lateral mesoderm [+]
Antibodies: Arl13b Ab3 Cdh1 Ab3 H3f3a Ab9 Nek2 Ab3 Nin Ab3 Nup98 Ab3 Tuba4b Ab5 Tubg1 Ab4 dsRed2 Ab1
Morpholinos: nek2 MO2 nek2 MO3 stk3 MO3

Disease Ontology terms: visceral heterotaxy [+]
OMIMs: HETEROTAXY, VISCERAL, 1, X-LINKED; HTX1

Article Images: [+] show captions
References [+] :
Bahe, Rootletin forms centriole-associated filaments and functions in centrosome cohesion. 2005, Pubmed


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