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Cell. 2019 Sep 5;178(6):1403-1420.e21. doi: 10.1016/j.cell.2019.08.019.

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

Author information

1
Stowers Institute for Medical Research, 1000E 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
2
Stowers Institute for Medical Research, 1000E 50(th) Street, Kansas City, MO 64110, USA.
3
Stowers Institute for Medical Research, 1000E 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. Electronic address: ksi@stowers.org.

Abstract

Prion-like proteins can assume distinct conformational and physical states in the same cell. Sequence analysis suggests that prion-like proteins are prevalent in various species; however, it remains unclear what functional space they occupy in multicellular organisms. Here, we report the identification of a prion-like protein, Herzog (CG5830), through a multimodal screen in Drosophila melanogaster. Herzog functions as a membrane-associated phosphatase and controls embryonic patterning, likely being involved in TGF-β/BMP and FGF/EGF signaling pathways. Remarkably, monomeric Herzog is enzymatically inactive and becomes active upon amyloid-like assembly. The prion-like domain of Herzog is necessary for both its assembly and membrane targeting. Removal of the prion-like domain impairs activity, while restoring assembly on the membrane using a heterologous prion-like domain and membrane-targeting motif can restore phosphatase activity. This study provides an example of a prion-like domain that allows an enzyme to gain essential functionality via amyloid-like assembly to control animal development.

KEYWORDS:

CG5830; Drosophila melanogaster; Herzog; Hzg; amyloid; embryo; patterning; phosphatase; prion-like protein; segment polarity

PMID:
31491385
DOI:
10.1016/j.cell.2019.08.019

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