The Enigmatic Role of Lipids in Cilia Signaling

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2020 Aug 28

PMID 32850869

Citations 14

Authors

Inna V Nechipurenko

Affiliations

Soon will be listed here.

Abstract

Primary cilia are specialized cellular structures that project from the surface of most cell types in metazoans and mediate transduction of major signaling pathways. The ciliary membrane is contiguous with the plasma membrane, yet it exhibits distinct protein and lipid composition, which is essential for ciliary function. Diffusion barriers at the base of a cilium are responsible for establishing unique molecular composition of this organelle. Although considerable progress has been made in identifying mechanisms of ciliary protein trafficking in and out of cilia, it remains largely unknown how the distinct lipid identity of the ciliary membrane is achieved. In this mini review, I summarize recent developments in characterizing lipid composition and organization of the ciliary membrane and discuss the emerging roles of lipids in modulating activity of ciliary signaling components including ion channels and G protein-coupled receptors.

Citing Articles

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References

DiTirro D, Philbrook A, Rubino K, Sengupta P . The Tubby homolog dynamically modulates olfactory cilia membrane morphogenesis and phospholipid composition. Elife. 2019; 8. PMC: 6624019. DOI: 10.7554/eLife.48789. View

Kumari S, Kumar A, Sardar P, Yadav M, Majhi R, Kumar A . Influence of membrane cholesterol in the molecular evolution and functional regulation of TRPV4. Biochem Biophys Res Commun. 2014; 456(1):312-9. DOI: 10.1016/j.bbrc.2014.11.077. View

Prosseda P, Luo N, Wang B, Alvarado J, Hu Y, Sun Y . Loss of OCRL increases ciliary PI(4,5)P in Lowe oculocerebrorenal syndrome. J Cell Sci. 2017; 130(20):3447-3454. PMC: 5665444. DOI: 10.1242/jcs.200857. View

Suh B, Hille B . PIP2 is a necessary cofactor for ion channel function: how and why?. Annu Rev Biophys. 2008; 37:175-95. PMC: 2692585. DOI: 10.1146/annurev.biophys.37.032807.125859. View

Raleigh D, Sever N, Choksi P, Sigg M, Hines K, Thompson B . Cilia-Associated Oxysterols Activate Smoothened. Mol Cell. 2018; 72(2):316-327.e5. PMC: 6503851. DOI: 10.1016/j.molcel.2018.08.034. View

Gahbauer S, Bockmann R . Membrane-Mediated Oligomerization of G Protein Coupled Receptors and Its Implications for GPCR Function. Front Physiol. 2016; 7:494. PMC: 5078798. DOI: 10.3389/fphys.2016.00494. View

Janich P, Corbeil D . GM1 and GM3 gangliosides highlight distinct lipid microdomains within the apical domain of epithelial cells. FEBS Lett. 2007; 581(9):1783-7. DOI: 10.1016/j.febslet.2007.03.065. View

Demmel L, Schmidt K, Lucast L, Havlicek K, Zankel A, Koestler T . The endocytic activity of the flagellar pocket in Trypanosoma brucei is regulated by an adjacent phosphatidylinositol phosphate kinase. J Cell Sci. 2014; 127(Pt 10):2351-64. PMC: 4021478. DOI: 10.1242/jcs.146894. View

Verhey K, Yang W . Permeability barriers for generating a unique ciliary protein and lipid composition. Curr Opin Cell Biol. 2016; 41:109-16. PMC: 4983468. DOI: 10.1016/j.ceb.2016.05.004. View

10.

Roberson E, Dowdle W, Ozanturk A, Garcia-Gonzalo F, Li C, Halbritter J . TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary transition zone. J Cell Biol. 2015; 209(1):129-42. PMC: 4395494. DOI: 10.1083/jcb.201411087. View

11.

Mukhopadhyay S, Wen X, Chih B, Nelson C, Lane W, Scales S . TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia. Genes Dev. 2010; 24(19):2180-93. PMC: 2947770. DOI: 10.1101/gad.1966210. View

12.

Vieira O, Gaus K, Verkade P, Fullekrug J, Vaz W, Simons K . FAPP2, cilium formation, and compartmentalization of the apical membrane in polarized Madin-Darby canine kidney (MDCK) cells. Proc Natl Acad Sci U S A. 2006; 103(49):18556-61. PMC: 1693701. DOI: 10.1073/pnas.0608291103. View

13.

Kiesel P, Alvarez Viar G, Tsoy N, Maraspini R, Gorilak P, Varga V . The molecular structure of mammalian primary cilia revealed by cryo-electron tomography. Nat Struct Mol Biol. 2020; 27(12):1115-1124. PMC: 7610599. DOI: 10.1038/s41594-020-0507-4. View

14.

Aveldano M, Bazan N . Molecular species of phosphatidylcholine, -ethanolamine, -serine, and -inositol in microsomal and photoreceptor membranes of bovine retina. J Lipid Res. 1983; 24(5):620-7. View

15.

Dyson J, Conduit S, Feeney S, Hakim S, DiTommaso T, Fulcher A . INPP5E regulates phosphoinositide-dependent cilia transition zone function. J Cell Biol. 2016; 216(1):247-263. PMC: 5223597. DOI: 10.1083/jcb.201511055. View

16.

Mostowy S, Cossart P . Septins: the fourth component of the cytoskeleton. Nat Rev Mol Cell Biol. 2012; 13(3):183-94. DOI: 10.1038/nrm3284. View

17.

Wingfield J, Lechtreck K, Lorentzen E . Trafficking of ciliary membrane proteins by the intraflagellar transport/BBSome machinery. Essays Biochem. 2018; 62(6):753-763. PMC: 6737936. DOI: 10.1042/EBC20180030. View

18.

Lemmon M . Membrane recognition by phospholipid-binding domains. Nat Rev Mol Cell Biol. 2008; 9(2):99-111. DOI: 10.1038/nrm2328. View

19.

Blacque O, Sanders A . Compartments within a compartment: what C. elegans can tell us about ciliary subdomain composition, biogenesis, function, and disease. Organogenesis. 2014; 10(1):126-37. PMC: 4049889. DOI: 10.4161/org.28830. View

20.

Chavez M, Ena S, Van Sande J, de Kerchove dExaerde A, Schurmans S, Schiffmann S . Modulation of Ciliary Phosphoinositide Content Regulates Trafficking and Sonic Hedgehog Signaling Output. Dev Cell. 2015; 34(3):338-50. DOI: 10.1016/j.devcel.2015.06.016. View