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. 2023 May 31;19(2):264–271. doi: 10.4103/1673-5374.377414

Figure 2.

Figure 2

The interplay between primary cilium, lipids, and autophagy.

The ciliary membrane contains exclusive lipids and receptors, which activate ciliary signaling pathways dependent on receptors and downstream scaffold proteins that localize at the primary cilium (PC). IFT-B mediates the anterograde ciliary trafficking of proteins to the tip of the PC using kinesin-2 motors, and IFT-A, together with dynein-2 motors, allow the retrograde transport of ciliary cargo to the PC basal body. Different lipid species are restricted to specific subdomains of ciliary membrane, where they are tightly regulated by enzymes that localize in proximity to their substrates and products (denoted by curved arrows). These lipids are required to maintain PC structure and function. Lipids can also modulate cargo ciliary trafficking and PC-dependent signaling pathways such as hedgehog-Ptch signaling at the PC, which are negatively affected by cholesterol accumulation in the lysosome of NPC1-deficient neurons. Cholesterol accumulation is correlated with PC dysfunction induced by impaired autophagy in these neurons. Conversely, ciliary signaling pathway can modulate the autophagic process, suggesting a bidirectional crosstalk between autophagy and ciliogenesis. For more information, please refer to the text. Created with BioRender.com. cAMP: Cyclic adenosine 3′–5′ monosphosphate; D2R: dopaminergic D2-receptors; GPCRs: G-protein-coupled receptors; IFT: intraflagellar transport; INPP5: inositol polyphosphate-5-phosphatase; IR: insulin receptor; LepRb: leptin receptor; MC4R: melanocortin 4 receptor; MCHR1: melanin-concentrating hormone receptor-1; NPC1: Niemann-Pick C1 protein; OCRL: oculocerebrorenal syndrome of Lowe protein; PI3K-C2α: phosphatidylinositol 3-kinase type 2α; PIP3: phosphatidylinositol (3,4,5)-trisphosphate; PIPKIγ: type Iγ phosphatidylinositol 4-phosphate 5-kinase; PKA: protein kinase A; Ptch: Patched; PtdIns: phosphatidylinositol; SSTR3: somatostatin receptor-3; TRPV4: transient receptor potential cation channel subfamily V member 4; TUB: tubby protein; TULP3: tubby-like protein 3.

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