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Amyloid-Like Assembly During Embryogenesis Activates Herzog, a Novel Prion-Like Phosphatase

99 Pages Posted: 25 Jan 2019 Sneak Peek Status: Published

See all articles by Zelha Nil

Zelha Nil

Stowers Institute for Medical Research; University of Kansas Medical Center - Department of Molecular and Integrative Physiology

Rubén Hervás Millán

Stowers Institute for Medical Research

Therese Gerbich

Stowers Institute for Medical Research

Paulo Leal

Stowers Institute for Medical Research

Zulin Yu

Stowers Institute for Medical Research

Anita Saraf

Stowers Institute for Medical Research

Mihaela Sardiu

Stowers Institute for Medical Research

Jeffrey J. Lange

Stowers Institute for Medical Research

Kexi Yi

Stowers Institute for Medical Research

Jay R. Unruh

Stowers Institute for Medical Research

Brian Slaughter

Stowers Institute for Medical Research

Kausik Si

Stowers Institute for Medical Research

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Abstract

Prion-like proteins can assume distinct conformational and physical states in the same cell. Sequence analysis suggests prion-like proteins are prevalent in various species, however it remains unclear what functional space they occupy in multicellular organisms. Here, we report a novel prion-like protein, Herzog (CG5830), identified through a multimodal screen in Drosophila melanogaster. Herzog functions as a membrane-associated phosphatase and controls embryonic patterning by acting on components of TGF-β/BMP and FGF/EGF signaling pathways. Remarkably, monomeric Herzog is enzymatically inactive and becomes active upon amyloid-like assembly during gastrulation. 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 a definitive example of a prion-like domain that allows an enzyme to gain essential functionality via amyloid-like assembly to control animal development.

Suggested Citation

Nil, Zelha and Millán, Rubén Hervás and Gerbich, Therese and Leal, Paulo and Yu, Zulin and Saraf, Anita and Sardiu, Mihaela and Lange, Jeffrey J. and Yi, Kexi and Unruh, Jay R. and Slaughter, Brian and Si, Kausik, Amyloid-Like Assembly During Embryogenesis Activates Herzog, a Novel Prion-Like Phosphatase. Available at SSRN: https://ssrn.com/abstract=3322363 or http://dx.doi.org/10.2139/ssrn.3322363
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Zelha Nil

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

University of Kansas Medical Center - Department of Molecular and Integrative Physiology

3901 Rainbow Boulevard
Kansas City, KS 66160
United States

Rubén Hervás Millán

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Therese Gerbich

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Paulo Leal

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Zulin Yu

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Anita Saraf

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Mihaela Sardiu

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Jeffrey J. Lange

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Kexi Yi

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Jay R. Unruh

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Brian Slaughter

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Kausik Si (Contact Author)

Stowers Institute for Medical Research ( email )

1000 E 50th Street
Kansas City, MO 64110
United States

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