The C. elegans Wnt/β-catenin Asymmetry (WβA) pathway utilizes asymmetric regulation of SYS-1/β-catenin and POP-1/TCF coactivators. WβA differentially regulates gene expression during cell fate decisions, specifically by asymmetric localization of determinants in mother cells to produce daughters biased towards their appropriate cell fate. Despite the induction of asymmetry, β-catenin localizes symmetrically to mitotic centrosomes in both mammals and C. elegans. Due to the mitosis-specific localization of SYS-1 to centrosomes and enrichment of SYS-1 at kinetochore microtubules when SYS-1 centrosomal loading is disrupted, we investigated active trafficking in SYS-1 centrosomal localization. Here, we demonstrate that trafficking by microtubule motor dynein is required to maintain SYS-1 centrosomal enrichment, by dynein RNAi-mediated decreases in SYS-1 centrosomal enrichment and by temperature-sensitive allele of the dynein heavy chain. Conversely, we observe depletion of microtubules by nocodazole treatment or RNAi of dynein-proteasome adapter ECPS-1 exhibits increased centrosomal enrichment of SYS-1. Moreover, disruptions to SYS-1 or negative regulator microtubule trafficking are sufficient to significantly exacerbate SYS-1 dependent cell fate misspecifications. We propose a model whereby retrograde microtubule-mediated trafficking enables SYS-1 enrichment at centrosomes, enhancing its eventual proteasomal degradation. These studies support the link between centrosomal localization and enhancement of proteasomal degradation, particularly for proteins not generally considered ‘centrosomal’.

Gout is a common crystal-induced arthropathy affecting mainly the joints of the appendicular skeleton; however, rarely this condition affects the axial skeleton as well. Spinal gout can cause radiculopathy, cord compression, canal stenosis and discitis. We describe a case of a 71-year-old woman where the initial presentation of destructive arthropathy and spinal masses secondary to axial gout was mistaken for a metastatic malignancy. Despite chronic polyarthropathy and bilateral subcutaneous gouty tophi, spinal gout was not considered a differential diagnosis during initial assessment.The patient was managed conservatively with pharmacological treatment resulting in improvement of her upper limb radiculopathy and systemic joint pain, although little improvement in mobility. Such extensive involvement is rare and the masses can mimic an underlying metastatic disease. Careful history and clinical examination recognising polyarthropathy and subcutaneous tophi can aid the clinician to make the right diagnosis and institute correct treatment. Delay in recognising gout as a differential diagnosis can lead to marked morbidity as illustrated in our case.

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The C. elegans Wnt/β-catenin Asymmetry (WβA) pathway utilizes asymmetric regulation of SYS-1/β-catenin and POP-1/TCF coactivators. This differentially regulates gene expression during cell fate decisions, specifically by asymmetric localization of determinants in mother cells to produce daughters biased towards their appropriate cell fate at birth. Despite the induction of asymmetry, β-catenin localizes symmetrically to mitotic centrosomes in both mammals and C. elegans. Due to the mitosis-specific mobility of centrosomal SYS-1 and ‘traffic jam’ like enrichment of SYS-1 at kinetochore microtubules when SYS-1 centrosomal loading is disrupted, we investigated active trafficking in SYS-1 centrosomal localization. Here, we demonstrate that trafficking by microtubule motor dynein is required to maintain SYS-1 centrosomal enrichment, by dynein RNAi-mediated decreases in SYS-1 centrosomal enrichment and by temperature-sensitive allele of the dynein heavy chain. Conversely, we observe that depletion of microtubules by Nocodazole treatment or RNAi of putative dynein-proteasome adapter ECPS-1 exhibits increased centrosomal enrichment of SYS-1. Moreover, disruptions to SYS-1 or negative regulator microtubule trafficking are sufficient to significantly exacerbate SYS-1 dependent cell fate misspecifications. We propose retrograde microtubule-mediated trafficking enables SYS-1 and negative regulators to enrich at centrosomes, enhancing their interaction and perhaps implicating the centrosome as a mitotic sink for proteins targeted for degradation.