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The PDZ protein Na+/H+ exchanger regulatory factor-1 (NHERF1) regulates planar cell polarity and motile cilia organization

Treat, AC and Wheeler, DS and Stolz, DB and Tsang, M and Friedman, P and Romero, G (2016) The PDZ protein Na+/H+ exchanger regulatory factor-1 (NHERF1) regulates planar cell polarity and motile cilia organization. PLoS ONE, 11 (4).

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© 2016 Treat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Directional flow of the cerebrospinal fluid requires coordinated movement of the motile cilia of the ependymal epithelium that lines the cerebral ventricles. Here we report that mice lacking the Na+/H+ Exchanger Regulatory Factor 1 (NHERF1/Slc9a3r1, also known as EBP50) develop profound communicating hydrocephalus associated with fewer and disorganized ependymal cilia. Knockdown of NHERF1/slc9a3r1 in zebrafish embryos also causes severe hydrocephalus of the hindbrain and impaired ciliogenesis in the otic vesicle. Ultrastructural analysis did not reveal defects in the shape or organization of individual cilia. Similar phenotypes have been described in animals with deficiencies in Wnt signaling and the Planar Cell Polarity (PCP) pathway. We show that NHERF1 binds the PCP core genes Frizzled (Fzd) and Vangl. We further show that NHERF1 assembles a ternary complex with Fzd4 and Vangl2 and promotes translocation of Vangl2 to the plasma membrane, in particular to the apical surface of ependymal cells. Taken together, these results strongly support an important role for NHERF1 in the regulation of PCP signaling and the development of functional motile cilia.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Treat, AC
Wheeler, DS
Stolz, DBdonna.stolz@pitt.eduDSTOLZ
Tsang, Mtsang@pitt.eduTSANG
Friedman, Ppaf10@pitt.eduPAF10
Romero, Gggr@pitt.eduGGR
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 April 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 11
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0153144
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Cell Biology
School of Medicine > Developmental Biology
School of Medicine > Pharmacology and Chemical Biology
School of Medicine > Structural Biology
Refereed: Yes
Date Deposited: 25 Aug 2016 17:20
Last Modified: 08 Jul 2019 17:55


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