Functional redundancy between Cdc14 phosphatases in zebrafish ciliogenesis

Abstract

Background: Cyclin-dependent kinases (Cdks) and their counteracting phosphatases are key regulators of cell cycle progression. In yeasts, the Cdc14 family of phosphatases promotes exit from mitosis and progression through cytokinesis by reversing phosphorylation of Cdk1 substrates. In vertebrates, CDC14 paralogs, CDC14A and CDC14B, have so far been implicated in processes ranging from DNA damage repair, meiosis, centrosome duplication to ciliogenesis. However, the question of whether CDC14 paralogs can functionally compensate for each other has yet to be addressed. Results: Here, using antisense morpholino oligonucleotides to inhibit Cdc14A1 function, we observed that Cdc14A1 depleted zebrafish embryos displayed ventrally curved body and left-right asymmetry defects, similar to Cdc14B deficient embryos and zebrafish mutants with cilia defects. Accordingly, we found that Cdc14A1, like Cdc14B, plays a role in ciliogenesis in the Kupffer's vesicle (KV) and other ciliated tissues, and can do so independently of its function in cell cycle. Furthermore, we observed reciprocal suppression of KV cilia length defects of Cdc14A1 and Cdc14B deficient embryos by cdc14b and cdc14a1 RNAs, respectively. Conclusions: Together, these studies demonstrate for the first time that Cdc14A and Cdc14B have overlapping functions in the ciliogenesis process during zebrafish development.

FgCDC14 regulates cytokinesis, morphogenesis, and pathogenesis in Fusarium graminearum

“…Basal bodies are microtubule organizing centers for flagella, while SPBs or centrioles are microtubule‐organizing centers for the mitotic spindle. Although the association of Cdc14 with basal bodies or motile cells have not been documented in Chytridiomycetes, Zebrafish Cdc14A1 phosphatase localizes to the base of the cilium, possibly in part at the basal body (Clement et al ., ) and PiCdc14 from the oomycete Phytophthora infestans accumulates at the basal body during zoospore formation (Ah‐Fong and Judelson, ). PiCdc14 binds microtubules in vitro and forms insoluble complexes in vivo .…”

Cdc14A and Cdc14B Redundantly Regulate DNA Double-Strand Break Repair

“…Recent functional studies in zebrafish showed redundant roles of the two vertebrate Cdc14 homologues, Cdc14A and Cdc14B, in ciliogenesis. Cdc14A-or Cdc14B-deficient zebrafish embryos displayed shorter cilia in Kupffer's vesicle, and the cilium length defects could be rescued by injection of Cdc14B or Cdc14A mRNA, respectively (7). In mammals, Cdc14A and Cdc14B appear to play roles in DNA repair (3,(8)(9)(10).…”

The human phosphatase CDC 14A modulates primary cilium length by regulating centrosomal actin nucleation

“…The cilia length phenotype was specific to hCDC14A and was not observed in cells lacking the paralogue hCDC14B. In contrast to RPE1 cells, cdc14A or cdc14B depletion in zebrafish led to shorter cilia , Presently, it is unclear why inactivation of CDC14A in zebrafish and human cells impacts cilia length in opposite ways. Variations in cilia phenotypes between organisms upon inactivation of orthologs have been reported before .…”