FGF Pyramus Has a Transmembrane Domain and Cell-Autonomous Function in Polarity

Area of Science:

• Developmental Biology
• Molecular Biology
• Cell Biology

Background:

• Fibroblast growth factors (FGFs) are crucial signaling molecules, typically acting as receptor ligands via a conserved FGF domain.
• Regions outside the FGF domain are variable and less understood, potentially harboring additional functions.
• Drosophila melanogaster possesses three FGF genes, including pyramus (pyr), which encode larger FGF proteins than typically observed.

Purpose of the Study:

• To investigate the functions of the Drosophila FGF protein, Pyramus (Pyr), focusing on its extended domains.
• To test the hypothesis that larger FGF proteins may represent ancestral forms with multiple functions within a single polypeptide.
• To elucidate the role of Pyr in cellular processes and organismal development.

Main Methods:

• Bioinformatic analysis to identify domains within the Pyr protein.
• Molecular biology techniques to create and analyze Pyr mutants, including degron deletion mutants.
• Phenotypic analysis of Pyr mutants during Drosophila development, focusing on gastrulation and cell polarity.

Main Results:

• Pyramus (Pyr) possesses a transmembrane domain (TMD) and an intracellular C-terminal domain with a degron.
• The intracellular domain regulates Pyr protein levels, while the TMD ensures precise spatial activation of the Heartless FGF receptor.
• Pyr mutants lacking the degron exhibit elevated Pyr levels, leading to cell polarity defects and invagination failures during gastrulation, indicating a cell-autonomous role.

Conclusions:

• Pyr is identified as the first transmembrane FGF, exhibiting both extracellular and intracellular functions.
• The spatial distribution and protein levels of Pyr are tightly regulated, crucial for proper embryonic development.
• These findings suggest that other FGFs may also be membrane-tethered or possess multifunctional properties, expanding the known roles of the FGF family.