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

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 h...

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Detalles Bibliográficos
Autores principales: Goto, Asako, Sakai, Shota, Mizuike, Aya, Yamaji, Toshiyuki, Hanada, Kentaro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254030/
https://www.ncbi.nlm.nih.gov/pubmed/35800758
http://dx.doi.org/10.1016/j.isci.2022.104624
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author Goto, Asako
Sakai, Shota
Mizuike, Aya
Yamaji, Toshiyuki
Hanada, Kentaro
author_facet Goto, Asako
Sakai, Shota
Mizuike, Aya
Yamaji, Toshiyuki
Hanada, Kentaro
author_sort Goto, Asako
collection PubMed
description 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.
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spelling pubmed-92540302022-07-06 Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide Goto, Asako Sakai, Shota Mizuike, Aya Yamaji, Toshiyuki Hanada, Kentaro iScience Article 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. Elsevier 2022-06-16 /pmc/articles/PMC9254030/ /pubmed/35800758 http://dx.doi.org/10.1016/j.isci.2022.104624 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Goto, Asako
Sakai, Shota
Mizuike, Aya
Yamaji, Toshiyuki
Hanada, Kentaro
Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide
title Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide
title_full Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide
title_fullStr Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide
title_full_unstemmed Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide
title_short Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide
title_sort compartmentalization of casein kinase 1 γ csnk1g controls the intracellular trafficking of ceramide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254030/
https://www.ncbi.nlm.nih.gov/pubmed/35800758
http://dx.doi.org/10.1016/j.isci.2022.104624
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