Regulated assembly of a prion-like phosphatase, CG5830, controls its phosphatase activity and embryonic development in Drosophila melanogaster

Abstract

Prion-like proteins can assume distinct conformational states in the same cell, and often one of these states leads to a self-assembling oligomer that can vary in physical nature. The conformational state change from monomers to oligomers can act like a switch, and most importantly this switch also leads to a change in protein function, i.e. loss of the original function or gain of a new function. Such protein switches have been shown to be involved in transcriptional regulation, translational regulation and signaling, regulating many different physiological processes such as stress response, memory formation, and immune response. However, it is unclear how common such mechanism(s) are utilized in multicellular organisms and the diversity of the processes they regulate. Here, I report the characterization of CG5830, a candidate a prion-like protein identified through a systematic screen in Drosophila melanogaster. I find that in the Drosophila embryo, CG5830 changes its conformational state from monomers to amyloid like oligomers on the membrane during gastrulation. It functions as a membrane phosphatase required for embryonic patterning and interacts with major regulators of developmental pathways, such as TGF-β, EGF and FGF signaling pathways. Finally, a conformational state change of CG5830 leads to gain of enzymatic function. My data indicate that prion-like protein switches can have essential roles in animal development.