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Updated: Mar 7, 2026
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Published on: October 19, 2006
Regulation of Drosophila Development by the Golgi Kinase Four-Jointed
Yoko Keira1, Moe Wada1, Hiroyuki O Ishikawa1
1Graduate School of Science, Chiba University, Chiba, Japan.
Abstract:
Despite intensive research on kinases and protein phosphorylation, most studies focus on kinases localized to the cytosol and nucleus. Studies in Drosophila discovered a novel signaling pathway that regulates growth and planar cell polarity. In this pathway, the atypical cadherin Fat acts as a receptor, and the cadherin Dachsous (Ds) serves as its ligand. Genetic studies in Drosophila identified the four-jointed gene as a regulator of the Fat pathway. Four-jointed (Fj) resides in the Golgi and phosphorylates the cadherin domains of Fat and Ds. Fj-mediated phosphorylations promote the ability of Fat to bind to its ligand Ds and inhibit the ability of Ds to bind Fat, which is biased toward a stronger effect on Fat. Fj is expressed in a gradient in many developing tissues. The Fat-Ds-binding gradient can be explained by the graded activity of Fj that is sufficient to propagate the polarization of complexes across whole tissues. Recent studies revealed a new class of kinases that localize within the secretory pathway and the extracellular space, and phosphorylate proteins and sugar chains in the secretory pathway. Further, they appear to regulate extracellular processes. Mutations of the genes encoding these kinases cause human disease, thus underscoring the biological importance of phosphorylation events within the secretory pathway.
Insights
A novel Golgi kinase, Four-jointed (Fj), regulates growth and cell polarity by phosphorylating cadherins. This phosphorylation controls Fat-Dachsous binding, impacting tissue polarization.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Most kinase research focuses on cytosolic and nuclear enzymes, neglecting the secretory pathway.
- A signaling pathway involving atypical cadherin Fat and its ligand Dachsous (Ds) regulates growth and planar cell polarity in Drosophila.
- The gene four-jointed (Fj) was identified as a regulator of the Fat pathway.
Purpose of the Study:
- To investigate the role of the Four-jointed (Fj) kinase in the Fat signaling pathway.
- To understand how Fj-mediated phosphorylation affects cadherin binding and tissue polarization.
Main Methods:
- Genetic studies in Drosophila to identify regulators of the Fat pathway.
- Analysis of Four-jointed (Fj) localization within the Golgi apparatus.
- Biochemical assays to determine Fj's effect on Fat and Dachsous (Ds) binding.
Main Results:
- Four-jointed (Fj) phosphorylates cadherin domains of Fat and Ds within the Golgi.
- Fj-mediated phosphorylation enhances Fat-Ds binding and inhibits Ds-Fat binding, with a stronger effect on Fat.
- Graded Fj activity explains the observed Fat-Ds binding gradients and tissue-wide polarization.
Conclusions:
- Four-jointed (Fj) is a key regulator of the Fat signaling pathway through extracellular cadherin phosphorylation.
- This study highlights the importance of kinases within the secretory pathway for developmental processes.
- Dysregulation of such kinases can lead to human diseases, emphasizing their biological significance.
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