Processing and phosphorylation of the Fat receptor.

Area of Science:

• Cell Biology
• Molecular Biology
• Developmental Biology

Background:

• The Drosophila tumor suppressors Fat and discs overgrown (dco) are crucial for regulating cell growth and polarity.
• Fat is a transmembrane receptor, but its post-translational modifications and regulatory mechanisms remain largely uncharacterized.

Purpose of the Study:

• To investigate the post-translational modifications of the Fat receptor.
• To elucidate the role of discs overgrown (dco) in Fat signaling and its impact on cellular processes.

Main Methods:

• Proteolytic processing analysis of Fat.
• Phosphorylation assays of the Fat intracellular domain in vitro and in vivo.
• Analysis of dco mutants to assess Fat signaling in growth, gene expression, and planar cell polarity.

Main Results:

• Fat undergoes constitutive proteolytic processing, forming a heterodimer of N- and C-terminal fragments at the cell surface.
• The cytoplasmic domain of Fat is phosphorylated, a process enhanced by the Fat ligand Dachsous and the kinase Dco.
• dco mutants disrupt Fat's influence on growth and gene expression but not its role in planar cell polarity.

Conclusions:

• Fat is subject to post-translational modifications including processing and phosphorylation.
• Dco promotes Fat phosphorylation, linking Dachsous-mediated activation to the Fat-Warts pathway.
• These findings deepen the understanding of Dco's requirement in Fat signaling pathways controlling growth and gene expression.