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XB-ART-51731
J Cell Biol December 7, 2015; 211 (5): 963-73.

The polarity protein Inturned links NPHP4 to Daam1 to control the subapical actin network in multiciliated cells.

Yasunaga T , Hoff S , Schell C , Helmstädter M , Kretz O , Kuechlin S , Yakulov TA , Engel C , Müller B , Bensch R , Ronneberger O , Huber TB , Lienkamp SS , Walz G .


Abstract
Motile cilia polarization requires intracellular anchorage to the cytoskeleton; however, the molecular machinery that supports this process remains elusive. We report that Inturned plays a central role in coordinating the interaction between cilia-associated proteins and actin-nucleation factors. We observed that knockdown of nphp4 in multiciliated cells of the Xenopus laevis epidermis compromised ciliogenesis and directional fluid flow. Depletion of nphp4 disrupted the subapical actin layer. Comparison to the structural defects caused by inturned depletion revealed striking similarities. Furthermore, coimmunoprecipitation assays demonstrated that the two proteins interact with each other and that Inturned mediates the formation of ternary protein complexes between NPHP4 and DAAM1. Knockdown of daam1, but not formin-2, resulted in similar disruption of the subapical actin web, whereas nphp4 depletion prevented the association of Inturned with the basal bodies. Thus, Inturned appears to function as an adaptor protein that couples cilia-associated molecules to actin-modifying proteins to rearrange the local actin cytoskeleton.

PubMed ID: 26644512
PMC ID: PMC4674276
Article link: J Cell Biol


Species referenced: Xenopus
Genes referenced: daam1 fmn1 fmn2 intu tub
Morpholinos: daam1 MO1 fmn1 MO1 fmn2 MO1 fmn2 MO2 intu MO1 nphp4.2 MO1 nphp4.2 MO2

Phenotypes: Xla Wt + daam1 MO (Fig. 4. B) [+]

Article Images: [+] show captions
References [+] :
Adler, Inturned localizes to the proximal side of wing cells under the instruction of upstream planar polarity proteins. 2004, Pubmed