Calcineurin associates with centrosomes and regulates cilia length maintenance.
Calcineurin
Centriole
Centrosome
Cilia
POC5
Phosphatase
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
15 04 2023
15 04 2023
Historique:
received:
18
06
2022
accepted:
27
03
2023
medline:
25
4
2023
pubmed:
5
4
2023
entrez:
4
4
2023
Statut:
ppublish
Résumé
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 expansion microscopy, 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.
Identifiants
pubmed: 37013443
pii: 307165
doi: 10.1242/jcs.260353
pmc: PMC10163345
pii:
doi:
Substances chimiques
Calcineurin
EC 3.1.3.16
Calcium
SY7Q814VUP
Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : K99 GM131024
Pays : United States
Organisme : NIGMS NIH HHS
ID : R00 GM131024
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM136243
Pays : United States
Organisme : NIH HHS
ID : R35 GM136243
Pays : United States
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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