Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide

Asako Goto; Shota Sakai; Aya Mizuike; Toshiyuki Yamaji; Kentaro Hanada

doi:10.1016/j.isci.2022.104624

Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide

iScience. 2022 Jun 16;25(7):104624. doi: 10.1016/j.isci.2022.104624. eCollection 2022 Jul 15.

Authors

Asako Goto¹, Shota Sakai¹, Aya Mizuike¹, Toshiyuki Yamaji¹, Kentaro Hanada¹

Affiliation

¹ Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.

Abstract

Casein 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 the C-terminal region of CK1G3 rendered the kinase hyperactive in cells. Deletion of the C-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 of C-terminal mutated CK1G1/2/3 similarly induced the multiple phosphorylation of the CERT SRM, thereby down-regulating de novo SM synthesis. These findings revealed that CK1Gs are regulated by a compartmentalization-based mechanism to access substrates present in specific intracellular organelles.

Keywords: Biological sciences; Cell biology; Functional aspects of cell biology.