The polarity protein Inturned links NPHP4 to Daam1 to control the subapical actin network in multiciliated cells
| Autor: | Gerd Walz, Barbara Müller, Martin Helmstädter, Sebastian Kuechlin, Christoph Schell, Soeren S. Lienkamp, Toma A. Yakulov, Oliver Kretz, Olaf Ronneberger, Tobias B. Huber, Takayuki Yasunaga, Christina Engel, Robert Bensch, Sylvia Hoff |
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| Rok vydání: | 2015 |
| Předmět: |
rho GTP-Binding Proteins
Green Fluorescent Proteins Molecular Sequence Data Oligonucleotides macromolecular substances Xenopus Proteins Biology Xenopus laevis Report Ciliogenesis Animals Humans Immunoprecipitation Cilia Cytoskeleton Research Articles Actin Adaptor Proteins Signal Transducing DAAM1 Microfilament Proteins Membrane Proteins Proteins Signal transducing adaptor protein Cell Biology Microfilament Protein Actin cytoskeleton Actins Basal Bodies Protein Structure Tertiary Cell biology Actin Cytoskeleton Drosophila melanogaster HEK293 Cells Gene Knockdown Techniques Motile cilium Epidermis Protein Binding |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.201502043 |
| Popis: | Inturned-mediated complex formation of NPHP4 and DAAM1 is important for ciliogenesis and ciliary function in multiciliated cells, presumably because of its requirement for the local rearrangement of actin cytoskeleton. 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. |
| Databáze: | OpenAIRE |
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