O-GlcNAcylation Regulates Primary Ciliary Length by Promoting Microtubule Disassembly

The sensory organelle cilium is involved in sensing and transducing important signaling cascades in almost all cells of our body. These ciliary-mediated pathways affect cellular homeostasis and metabolisms profoundly. However, it is almost completely unknown whether the cellular metabolic state affects the assembly of cilia. This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length. Pharmacologic or genetic inhibition of O-GlcNAcylation led to longer cilia, and vice versa. Further biochemical assays revealed that both α-tubulin and HDAC6 (histone deacetylase 6) were O-GlcNAcylated in vivo. In vitro enzymatic assays showed that O-GlcNAcylation of either tubulin or HDAC6 promoted microtubule disassembly, which likely in turn caused ciliary shortening. Taken together, these results uncovered a negative regulatory role of O-GlcNAc in modulating the ciliary microtubule assembly. The cross talk between O-GlcNAc and cilium is likely critical for fine-tuning the cellular response to nutrients.