Palmitoylation targets the calcineurin phosphatase to the phosphatidylinositol 4-kinase complex at the plasma membrane

Idil Ulengin-Talkish, Matthew A. H. Parson, Meredith L. Jenkins, Jagoree Roy, Alexis Z. L. Shih, Nicole St-Denis, Gergo Gulyas, Tamas Balla, Anne-Claude Gingras, Péter Várnai, Elizabeth Conibear, John E. Burke and Martha S. Cyert ()
Additional contact information
Idil Ulengin-Talkish: Stanford University
Matthew A. H. Parson: Department of Biochemistry and Microbiology, University of Victoria
Meredith L. Jenkins: Department of Biochemistry and Microbiology, University of Victoria
Jagoree Roy: Stanford University
Alexis Z. L. Shih: University of British Columbia
Nicole St-Denis: University of Toronto
Gergo Gulyas: National Institutes of Health
Tamas Balla: National Institutes of Health
Anne-Claude Gingras: University of Toronto
Péter Várnai: Semmelweis University
Elizabeth Conibear: University of British Columbia
John E. Burke: Department of Biochemistry and Microbiology, University of Victoria
Martha S. Cyert: Stanford University

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract Calcineurin, the conserved protein phosphatase and target of immunosuppressants, is a critical mediator of Ca2+ signaling. Here, to discover calcineurin-regulated processes we examined an understudied isoform, CNAβ1. We show that unlike canonical cytosolic calcineurin, CNAβ1 localizes to the plasma membrane and Golgi due to palmitoylation of its divergent C-terminal tail, which is reversed by the ABHD17A depalmitoylase. Palmitoylation targets CNAβ1 to a distinct set of membrane-associated interactors including the phosphatidylinositol 4-kinase (PI4KA) complex containing EFR3B, PI4KA, TTC7B and FAM126A. Hydrogen-deuterium exchange reveals multiple calcineurin-PI4KA complex contacts, including a calcineurin-binding peptide motif in the disordered tail of FAM126A, which we establish as a calcineurin substrate. Calcineurin inhibitors decrease PI4P production during Gq-coupled GPCR signaling, suggesting that calcineurin dephosphorylates and promotes PI4KA complex activity. In sum, this work discovers a calcineurin-regulated signaling pathway which highlights the PI4KA complex as a regulatory target and reveals that dynamic palmitoylation confers unique localization, substrate specificity and regulation to CNAβ1.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26326-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26326-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26326-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().