Calcineurin associates with centrosomes and regulates cilia length maintenance
Calcineurin, or PP2B, the Ca2+ and calmodulin-activated phosphatase and target of immunosuppressants, has many substrates and functions that remain undiscovered. By combining rapid proximity-dependent labeling with cell cycle synchronization, we mapped calcineurins spatial distribution in different cell cycle stages. While calcineurin-proximal proteins did not vary significantly between interphase and mitosis, calcineurin consistently associated with multiple centrosomal/ciliary proteins. These include POC5, which binds centrin 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 expansion microscopy, we demonstrate that calcineurin co-localizes with POC5 at the centrosome, and further show that calcineurin inhibitors alter POC5 distribution within the centriole lumen. Our discovery that calcineurin directly associates with centrosomal proteins highlights a role for Ca2+ and calcineurin signaling at these organelles. Calcineurin inhibition promotes primary cilia elongation without affecting ciliogenesis. Thus, Ca2+ signaling within cilia includes previously unknown functions for calcineurin in cilia length maintenance, a process frequently disrupted in ciliopathies. Summary statementCalcineurin phosphatase participates in centrosome and cilia regulation. Calcineurin localizes to centrosomes, where it interacts with partner POC5, and its inhibition promotes cilia elongation.