The PDZ Protein Na+/H+ Exchanger Regulatory Factor-1 (NHERF1) Regulates Planar Cell Polarity and Motile Cilia Organization.

Abstract	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.
Authors	Anny Caceres Treat, David S Wheeler, Donna B Stolz, Michael Tsang, Peter A Friedman, Guillermo Romero
Journal	PloS one (PLoS One) Vol. 11 Issue 4 Pg. e0153144 ( 2016) ISSN: 1932-6203 [Electronic] United States
PMID	27055101 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Phosphoproteins Sodium-Hydrogen Exchangers sodium-hydrogen exchanger regulatory factor
Topics	Animals CHO Cells Cell Polarity Cilia (physiology, ultrastructure) Cricetulus Gene Knockdown Techniques Hydrocephalus (genetics, veterinary) Mice Phosphoproteins (chemistry, genetics, metabolism) Sodium-Hydrogen Exchangers (chemistry, genetics, metabolism) Wnt Signaling Pathway Zebrafish

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