The Polarity Protein Inturned Links NPHP4 to Daam1 to Control the Subapical Actin Network in Multiciliated Cells

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2015 Dec 9

PMID 26644512

Citations 32

Authors

Takayuki Yasunaga

Sylvia Hoff

Christoph Schell

Martin Helmstadter

Oliver Kretz

Sebastian Kuechlin

Toma A Yakulov

Christina Engel

Barbara Muller

Robert Bensch

Olaf Ronneberger

Tobias B Huber

Soeren S Lienkamp

Gerd Walz

Affiliations

Soon will be listed here.

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.

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