Amyloid-like Assembly Activates a Phosphatase in the Developing Drosophila Embryo

Area of Science:

• Molecular Biology
• Developmental Biology
• Biochemistry

Background:

• Prion-like proteins exhibit diverse conformational states within cells.
• The functional roles of these proteins in multicellular organisms are not fully understood.

Purpose of the Study:

• To identify and characterize novel prion-like proteins in multicellular organisms.
• To elucidate the functional mechanism of the identified prion-like protein, Herzog, in embryonic development.

Main Methods:

• Multimodal screening in Drosophila melanogaster to identify Herzog (CG5830).
• Biochemical assays to determine Herzog's enzymatic activity and assembly properties.
• Genetic manipulation to assess the role of the prion-like domain in Herzog's function.

Main Results:

• Herzog identified as a membrane-associated phosphatase controlling embryonic patterning.
• Enzymatic activity of Herzog is dependent on amyloid-like assembly; monomers are inactive.
• The prion-like domain is essential for Herzog assembly and membrane localization, and its activity can be restored by re-establishing assembly on the membrane.

Conclusions:

• Prion-like domains can enable enzymes to acquire essential functionality through amyloid-like assembly.
• Herzog's assembly-dependent activity is critical for regulating key signaling pathways (TGF-β/BMP, FGF/EGF) during animal development.