Summary 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.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder caused by ATTCT expansion in the ATXN10 gene. Previous investigations have identified that depletion of Ataxin-10, the gene product, leads to cellular apoptosis and cytokinesis failure. Herein we identify the mitotic kinase Aurora B as an Ataxin-10 interacting partner. Aurora B interacts with and phosphorylates Ataxin-10 at S12, as evidenced by in vitro kinase and mass spectrometry analysis. Both endogenous and S12-phosphorylated Ataxin-10 localizes to the midbody during cytokinesis, and cytokinetic defects induced by inhibition of ATXN10 expression is not rescued by the S12A mutant. Inhibition of Aurora B or expression of the S12A mutant renders reduced interaction between Ataxin-10 and polo-like kinase 1 (Plk1), a kinase previously identified to regulate Ataxin-10 in cytokinesis. Taken together, we propose a model that Aurora B phosphorylates Ataxin-10 at S12 to promote the interaction between Ataxin-10 and Plk1 in cytokinesis. These findings identify an Aurora B-dependent mechanism that implicates Ataxin-10 in cytokinesis.

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The development of multifunctional nanoprobes for simultaneous targeted imaging, tumor boundary identification and photothermal therapy of gastric cancer has become a great challenge. Herein, EGFR monoclonal antibody-conjugated Au@Ag nanorods decorated with DTNB nanoprobes (5,5'-Dithiobis-(2-nitrobenzoic acid)) (EGFR-Au@Ag NR nanotags) were prepared and characterized. Their biocompatibility was analyzed by MTT assay. In vitro studies show that EGFR-Au@Ag NR nanotags own good biocompatibility and capability of targeting and entering into gastric cancer MGC803 cells, silver nano-film layer on the surface of gold nanorods remarkably enhance surfaceenhanced rama spectra (SERS) signal, enhanced photoacoustic imaging efficacy and photothermal conversion efficiency of gold nanorods. In vivo studies show that prepared nanotags could target actively gastric cancer cells at 2 h post-injection, and distributed in the tumor site, exhibited enhanced SERS signals to display clearly tumor boundary, enhanced photoacoustic imaging to display clearly tumor boundary. Under 1 w/cm 2 laser irradiation, tumor growth was remarkably inhibited by local photothermal therapy. In conclusion, high performance EGFR-antibody conjugated Au@Ag nanorod-DTNB nanoprobes exhibit great potential in applications such as targeted photoacoustic imaging, simultaneous tumor boundary identification and selective photothermal therapy of gastric cancer in the near future.