First Author | Greer YE | Year | 2011 |
Journal | J Cell Biol | Volume | 192 |
Issue | 6 | Pages | 993-1004 |
PubMed ID | 21422228 | Mgi Jnum | J:169860 |
Mgi Id | MGI:4943363 | Doi | 10.1083/jcb.201011111 |
Citation | Greer YE, et al. (2011) Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth. J Cell Biol 192(6):993-1004 |
abstractText | Previously we determined that Dishevelled-2/3 (Dvl) mediate Wnt-3a-dependent neurite outgrowth in Ewing sarcoma family tumor cells. Here we report that neurite extension was associated with Dvl phosphorylation and that both were inhibited by the casein kinase 1 (CK1) delta/epsilon inhibitor IC261. Small interfering RNAs targeting either CK1delta or CK1epsilon decreased Dvl phosphorylation, but only knockdown of CK1delta blocked neurite outgrowth. CK1delta but not CK1epsilon was detected at the centrosome, an organelle associated with neurite formation. Deletion analysis mapped the centrosomal localization signal (CLS) of CK1delta to its C-terminal domain. A fusion protein containing the CLS and EGFP displaced full-length CK1delta from the centrosome and inhibited Wnt-3a-dependent neurite outgrowth. In contrast to wild-type CK1epsilon, a chimera comprised of the kinase domain of CK1epsilon and the CLS of CK1delta localized to the centrosome and rescued Wnt-3a-dependent neurite outgrowth suppressed by CK1delta knockdown. These results provide strong evidence that the centrosomal localization of CK1delta is required for Wnt-3a-dependent neuritogenesis. |