Calcineurin associates with centrosomes and regulates cilia length maintenance

Eirini Tsekitsidou, Cassandra J. Wong, Idil Ulengin-Talkish, Angela I.M. Barth, Tim Stearns, Anne Claude Gingras, Jennifer T. Wang, Martha S. Cyert

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Calcineurin, or protein phosphatase 2B (PP2B), the Ca2+ and calmodulin-activated phosphatase and target of immunosuppressants, has many substrates and functions that remain uncharacterized. By combining rapid proximity-dependent labeling with cell cycle synchronization, we mapped the spatial distribution of calcineurin in different cell cycle stages. While calcineurin-proximal proteins did not vary significantly between interphase and mitosis, calcineurin consistently associated with multiple centrosomal and/or ciliary proteins. These include POC5, which binds centrins in a Ca2+-dependent manner and is a component of the luminal scaffold that stabilizes centrioles. We show that POC5 contains a calcineurin substrate motif (PxIxIT type) that mediates calcineurin binding in vivo and in vitro. Using indirect immunofluorescence and ultrastructure expansionmicroscopy, we demonstrate that calcineurin colocalizes with POC5 at the centriole, and further show that calcineurin inhibitors alter POC5 distribution within the centriole lumen. Our discovery that calcineurin directly associates with centriolar proteins highlights a role for Ca2+ and calcineurin signaling at these organelles. Calcineurin inhibition promotes elongation of primary cilia without affecting ciliogenesis. Thus, Ca2+ signaling within cilia includes previously unknown functions for calcineurin in maintenance of cilia length, a process that is frequently disrupted in ciliopathies.

Original languageEnglish
Article numberjcs260353
JournalJournal of cell science
Volume136
Issue number8
DOIs
StatePublished - Apr 2023

Keywords

  • Calcineurin
  • Centriole
  • Centrosome
  • Cilia
  • POC5
  • Phosphatase

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