Neurite Outgrowth of Mature Retinal Ganglion Cells and PC12 Cells Requires Activity of CK1δ and CK1ε

Department of General, Visceral and Transplantation Surgery, University of Ulm, Ulm, Germany.
PLoS ONE (Impact Factor: 3.23). 06/2011; 6(6):e20857. DOI: 10.1371/journal.pone.0020857
Source: PubMed


Mature retinal ganglion cells (RGCs) do not normally regenerate severed axons after optic nerve injury and show only little neurite outgrowth in culture. However, RGCs can be transformed into an active regenerative state after lens injury (LI) enabling these neurons to regrow axons in vitro and in vivo. In the current study we investigated the role of CK1δ and CK1ε activity in neurite outgrowth of LI stimulated RGCs and nerve growth factor (NGF) stimulated PC12 cells, respectively. In both cell types CK1δ and ε were localized in granular particles aligned at microtubules in neurites and growth cones. Although LI treatment did not measurably affect the expression of CK1δ and ε, it significantly elevated the specific kinase activity in the retina. Similarly, CK1δ/ε specific kinase activity was also elevated in NGF treated PC12 cells compared with untreated controls. Neurite extension in PC12 cells was associated with a change in the activity of CK1δ C-terminal targeting kinases, suggesting that activity of these kinases might be necessary for neurite outgrowth. Pharmacological inactivation of CK1δ and ε markedly compromised neurite outgrowth of both, PC12 cells and LI stimulated RGCs in a concentration dependent manner. These data provide evidence for a so far unknown, but essential role of CK1 isoforms in neurite growth.

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    • "CKIα, δ, and ε involved in vesicular trafficking [16–18] are also implicated in canonical Wnt signaling, but with distinct role [19]. CKIδ transduces specific centrosome functions [20], but, like CKIε, it also contributes to the regulation of the circadian rhythm [21, 22], apoptosis [23], and neuronal neurite outgrowth [24]. Interestingly, among the CKI family, the closely related CKIγ proteins (CKIγ1, 2, and 3) are unique in carrying C-terminal lipid modification motif that is believed to anchor them at the plasma membrane [25, 26]. "
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