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LRP2 contributes to planar cell polarity-dependent coordination of motile cilia function

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Item Type:Article
Title:LRP2 contributes to planar cell polarity-dependent coordination of motile cilia function
Creators Name:Bunatyan, L. and Margineanu, A. and Boutin, C. and Montcouquiol, M. and Bachmann, S. and Christensen, E.I. and Willnow, T.E. and Christ, A.
Abstract:Motile cilia are protruding organelles on specialized epithelia that beat in a synchronous fashion to propel extracellular fluids. Coordination and orientation of cilia beating on individual cells and across tissues is a complex process dependent on planar cell polarity (PCP) signaling. Asymmetric sorting of PCP pathway components, essential to establish planar polarity, involves trafficking along the endocytic path, but the underlying regulatory processes remain incompletely understood. Here, we identified the endocytic receptor LRP2 as regulator of PCP component trafficking in ependyma, a multi-ciliated cell type that is involved in facilitating flow of the cerebrospinal fluid in the brain ventricular system. Lack of receptor expression in gene-targeted mice results in a failure to sort PCP core proteins to the anterior or posterior cell side and, consequently, in the inability to coordinate cilia arrangement and to aligned beating (loss of rotational and translational polarity). LRP2 deficiency coincides with a failure to sort NHERF1, a cytoplasmic LRP2 adaptor to the anterior cell side. As NHERF1 is essential to translocate PCP core protein Vangl2 to the plasma membrane, these data suggest a molecular mechanism whereby LRP2 interacts with PCP components through NHERF1 to control their asymmetric sorting along the endocytic path. Taken together, our findings identified the endocytic receptor LRP2 as a novel regulator of endosomal trafficking of PCP proteins, ensuring their asymmetric partition and establishment of translational and rotational planar cell polarity in the ependyma.
Keywords:Planar Cell Polarity (PCP) Signaling, Motile Cilia, NHERF1, LRP2, Endocytosis, Animals, Mice
Source:Cell and Tissue Research
ISSN:0302-766X
Publisher:Springer
Volume:392
Number:2
Page Range:535-551
Date:May 2023
Official Publication:https://doi.org/10.1007/s00441-023-03757-7
PubMed:View item in PubMed
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https://edoc.mdc-berlin.de/21791/Preprint version

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