摘要：SummaryCasein kinase 1 γ (CK1G) is involved in the regulation of various cellular functions. For instance, the ceramide transport protein (CERT), which delivers ceramide to the Golgi apparatus for the synthesis of sphingomyelin (SM), is inactivated when it receives multiple phosphorylation by CK1G. Using human genome-wide gene disruption screening with an SM-binding cytolysin, we found that loss of theC-terminal region of CK1G3 rendered the kinase hyperactive in cells. Deletion of theC-terminal 20 amino acids or mutation of cysteine residues expected to be palmitoylated sites redistributed CK1G3 from cytoplasmic punctate compartments to the nucleocytoplasm. Wild-type CK1G3 exhibited a similar redistribution in the presence of 2-bromopalmitate, a protein palmitoylation inhibitor. Expression ofC-terminal mutated CK1G1/2/3 similarly induced the multiple phosphorylation of the CERT SRM, thereby down-regulatingde novoSM synthesis. These findings revealed that CK1Gs are regulated by a compartmentalization-based mechanism to access substrates present in specific intracellular organelles.Graphical abstractDisplay OmittedHighlights•C-terminal region of CSNK1Gs restricts their localization to punctate compartments•Loss of the kinase compartmentalization causes hyperphosphorylation of CERT•Compartmentalization of CSNK1G controls ceramide transport andde novoSM synthesisBiological sciences; Cell biology; Functional aspects of cell biology
