Primary cilia and lipid raft dynamics.

Yuhei Nishimura,Masaki Inagaki,Katsunori Uchida,Masatoshi Watanabe,Takashi Shiromizu,Daishi Yamakawa

doi:10.1098/rsob.210130

Abstract

Primary cilia, antenna-like structures of the plasma membrane, detect various extracellular cues and transduce signals into the cell to regulate a wide range of functions. Lipid rafts, plasma membrane microdomains enriched in cholesterol, sphingolipids and specific proteins, are also signalling hubs involved in a myriad of physiological functions. Although impairment of primary cilia and lipid rafts is associated with various diseases, the relationship between primary cilia and lipid rafts is poorly understood. Here, we review a newly discovered interaction between primary cilia and lipid raft dynamics that occurs during Akt signalling in adipogenesis. We also discuss the relationship between primary cilia and lipid raft-mediated Akt signalling in cancer biology. This review provides a novel perspective on primary cilia in the regulation of lipid raft dynamics.

Highlights

Primary cilia are non-motile, 1–10 μm long antenna-like structures observed in a variety of vertebrate cells
receptor tyrosine kinases (RTKs), such as insulin receptor (IR), IGF1 receptor (IGF1R), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR) and plateletderived growth factor receptor (PDGFR), are transmembrane proteins that are activated by ligand binding, which usually causes dimerization and/or oligomerization of the receptors followed by trans-autophosphorylation of multiple tyrosine residues [28]
We found that lipid raft dynamics were impaired in C3H10T1/2 cells with Tchp KD, in which the primary cilia were elongated, but not in C3H10T1/2 cells with double KD of Tchp and Ift88, in which the elongation of primary cilia caused by Tchp KD was suppressed by concomitant KD of Ift88, resulting in primary cilia being of similar length to that of control C3H10T1/2 cells [27]

Summary

Introduction

Primary cilia are non-motile, 1–10 μm long antenna-like structures observed in a variety of vertebrate cells. PIP3 binds to the pleckstrin homology domain of Akt, promoting the binding of Akt to phosphatidylinositol-dependent protein 1 (PDK1) and mammalian target of rapamycin complex (mTORC), which phosphorylate Thr308 and Ser473 of Akt, respectively All these components are located in lipid rafts, increasing the efficiency of Akt activation. Phosphorylated Akt regulates downstream signalling proteins in fundamental cellular functions, whereas over-activation of lipid raft-mediated Akt signalling is associated with various metabolic diseases [22,23]. Both primary cilia and lipid rafts act as signalling hubs, their relationship has been poorly understood. We discuss potential therapeutic approaches for obesity and cancer targeting lipid raft dynamics and primary cilia

Lipid rafts in the regulation of RTKs signalling

Primary cilia and lipid raft-mediated Akt signalling in cancer biology

Therapeutic approaches targeting lipid raft dynamics through primary cilia

98. Coelho PA et al 2015 Over-expression of Plk4