| First Author | Agassandian M | Year | 2012 |
| Journal | Mol Biol Cell | Volume | 23 |
| Issue | 14 | Pages | 2755-69 |
| PubMed ID | 22621903 | Mgi Jnum | J:198762 |
| Mgi Id | MGI:5499087 | Doi | 10.1091/mbc.E11-10-0863 |
| Citation | Agassandian M, et al. (2012) Calcium-calmodulin kinase I cooperatively regulates nucleocytoplasmic shuttling of CCTalpha by accessing a nuclear export signal. Mol Biol Cell 23(14):2755-69 |
| abstractText | We identified a new calmodulin kinase I (CaMKI) substrate, cytidyltransferase (CCTalpha), a crucial enzyme required for maintenance of cell membranes. CCTalpha becomes activated with translocation from the cytoplasm to the nuclear membrane, resulting in increased membrane phospholipids. Calcium-activated CCTalpha nuclear import is mediated by binding of its C-terminus to 14-3-3 zeta, a regulator of nuclear trafficking. Here CaMK1 phosphorylates residues within this C-terminus that signals association of CCTalpha with 14-3-3 zeta to initiate calcium-induced nuclear entry. CaMKI docks within the CCTalpha membrane-binding domain (residues 290-299), a sequence that displays similarities to a canonical nuclear export signal (NES) that also binds CRM1/exportin 1. Expression of a CFP-CCTalpha mutant lacking residues 290-299 in cells results in cytosolically retained enzyme. CRM1/exportin 1 was required for CCTalpha nuclear export, and its overexpression in cells was partially sufficient to trigger CCTalpha nuclear export despite calcium stimulation. An isolated CFP-290-299 peptide remained in the nucleus in the presence of leptomycin B but was able to target to the cytoplasm with farnesol. Thus CaMKI vies with CRM1/exportin 1 for access to a NES, and assembly of a CaMKI-14-3-3 zeta-CCTalpha complex is a key effector mechanism that drives nuclear CCTalpha translocation. |
