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Retinal ganglion cells (RGCs) do not normally regenerate axons into the lesioned optic nerve. However, RGCs can be transformed into an active regenerative state after lens injury (LI) enabling these neurons to regenerate neurites in vivo and in vitro. In the current study we investigated the role of CK1δ/є activity in neurite outgrowth of LI stimulated RGCs and PC12 cells after differentiation by nerve growth factor. In both cell types CK1δ/є was localized in granular particles aligned at microtubules in neurites and in the growth cone. Although CK1δ/є expression was not measurably increased after LI treatment in the retina and only CK1δ expression transiently and slightly elevated in differentiated PC12 cells, CK1δ/є specific kinase activity was significantly higher in neurite-growing PC12 cells. Furthermore, neurite outgrowth in PC12 cells was associated with a change in the activity of CK1δ C-terminal targeting kinases. Inhibition of CK1δ/є activity strongly compromised neurite outgrowth of both, PC12 and cultured RGCs in a concentration dependent manner. At higher concentrations inhibition of CK1δ/є activity caused a complete retraction of neurites without affecting the cell body. These data provide evidence for a so far unknown, but essential role of CK1δ/є in neurite growth. [ABSTRACT FROM AUTHOR]

Adiponectin, a hormone produced and secreted by adipocytes, modulates a number of metabolic processes, including glucose regulation, homeostasis, and fatty acid catabolism. It plays an important role in the suppression of the metabolic derangements that may result in type 2 diabetes, atherosclerosis and non-alcoholic fatty liver disease. Posttranslational modifications such as hydroxylation and glycosylation are important for regulating the activity of adiponectin since they influence the formation of high active multimeric complexes. In this study we addressed the role of reversible phosphorylation in modulating the activity of adiponectin. We showed that adiponectin is phosphorylated in vitro by several kinases, among them casein kinase 1 delta (CK1δ). CK1δ preferentially phosphorylates adiponectin within the globular domain. The formation of multimeric adiponectin complexes was increased by phosphatase treatment in vitro. Furthermore, specific inhibition of CK1δ by IC261 promotes the formation of higher molecular weight (HMW) complexes in human adipocytes. In summary, our data provide evidence that adiponectin is a phosphoprotein. Its reversible phosphorylation, especially at sites targeted by CK1δ in vitro, provides another regulatory mechanism to modulate complex formation and activity of adiponectin. [ABSTRACT FROM AUTHOR]