NDR kinase tricornered genetically interacts with Ccm3 and metabolic enzymes in Drosophila melanogaster tracheal development

Hudson, J; Paul, S; Veraksa, A; Ghabrial, A; Harvey, KF; Poon, C

Author(s): Hudson, J; Paul, S; Veraksa, A; Ghabrial, A; Harvey, KF; Poon, C;
Details: Publication Year 2023-03-09,Volume 13,Issue #3,Page jkad013
Journal Title: G3
Publication Type: Research article
Abstract: The Germinal Center Kinase III (GckIII) pathway is a Hippo-like kinase module defined by sequential activation of Ste20 kinases Thousand and One (Tao) and GckIII, followed by nuclear dbf2-related (NDR) kinase Tricornered (Trc). We previously uncovered a role for the GckIII pathway in Drosophila melanogaster tracheal (respiratory) tube morphology. The trachea form a network of branched epithelial tubes essential for oxygen transport, and are structurally analogous to branched tubular organs in vertebrates, such as the vascular system. In the absence of GckIII pathway function, aberrant dilations form in tracheal tubes characterized by mislocalized junctional and apical proteins, suggesting that the pathway is important in maintaining tube integrity in development. Here, we observed a genetic interaction between trc and Cerebral cavernous malformations 3 (Ccm3), the Drosophila ortholog of a human vascular disease gene, supporting our hypothesis that the GckIII pathway functions downstream of Ccm3 in trachea, and potentially in the vertebrate cerebral vasculature. However, how GckIII pathway signaling is regulated and the mechanisms that underpin its function in tracheal development are unknown. We undertook biochemical and genetic approaches to identify proteins that interact with Trc, the most downstream GckIII pathway kinase. We found that known GckIII and NDR scaffold proteins are likely to control GckIII pathway signaling in tracheal development, consistent with their conserved roles in Hippo-like modules. Furthermore, we show genetic interactions between trc and multiple enzymes in glycolysis and oxidative phosphorylation, suggesting a potential function of the GckIII pathway in integrating cellular energy requirements with maintenance of tube integrity.
Publisher: Oxford University Press
Keywords: Animals; Humans; Drosophila melanogaster/genetics/metabolism; *Drosophila Proteins/genetics/metabolism; Germinal Center Kinases/genetics/metabolism; *Protein Serine-Threonine Kinases/genetics/metabolism; Signal Transduction; Ccm3; Ndr; hippo-like; metabolism; trachea
Department(s): Laboratory Research
PubMed ID: 36653023
Publisher's Version: https://doi.org/10.1093/g3journal/jkad013
Open Access at Publisher's Site: https://doi.org/10.1093/g3journal/jkad013
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-06-27 07:58:58

Last Modified: 2023-06-27 07:59:22