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Proc Natl Acad Sci U S A January 1, 2020; 117 (24): 13571-13579.

CAMSAP3 facilitates basal body polarity and the formation of the central pair of microtubules in motile cilia.

Robinson AM , Takahashi S , Brotslaw EJ , Ahmad A , Ferrer E , Procissi D , Richter CP , Cheatham MA , Mitchell BJ , Zheng J .

Synchronized beating of cilia on multiciliated cells (MCCs) generates a directional flow of mucus across epithelia. This motility requires a "9 + 2" microtubule (MT) configuration in axonemes and the unidirectional array of basal bodies of cilia on the MCCs. However, it is not fully understood what components are needed for central MT-pair assembly as they are not continuous with basal bodies in contrast to the nine outer MT doublets. In this study, we discovered that a homozygous knockdown mouse model for MT minus-end regulator calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), Camsap3 tm1a/tm1a , exhibited multiple phenotypes, some of which are typical of primary ciliary dyskinesia (PCD), a condition caused by motile cilia defects. Anatomical examination of Camsap3 tm1a/tm1a mice revealed severe nasal airway blockage and abnormal ciliary morphologies in nasal MCCs. MCCs from different tissues exhibited defective synchronized beating and ineffective generation of directional flow likely underlying the PCD-like phenotypes. In normal mice, CAMSAP3 localized to the base of axonemes and at the basal bodies in MCCs. However, in Camsap3 tm1a/tm1a , MCCs lacked CAMSAP3 at the ciliary base. Importantly, the central MT pairs were missing in the majority of cilia, and the polarity of the basal bodies was disorganized. These phenotypes were further confirmed in MCCs of Xenopus embryos when CAMSAP3 expression was knocked down by morpholino injection. Taken together, we identified CAMSAP3 as being important for the formation of central MT pairs, proper orientation of basal bodies, and synchronized beating of motile cilia.

PubMed ID: 32482850
PMC ID: PMC7306751
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Species referenced: Xenopus
Genes referenced: camsap3 kidins220 mcc slc22a18 tub
Morpholinos: camsap3 MO1

Disease Ontology terms: primary ciliary dyskinesia
Phenotypes: Xla + camsap3 MO (Fig. 4B) [+]

Article Images: [+] show captions
References [+] :
Boutin, A dual role for planar cell polarity genes in ciliated cells. 2014, Pubmed