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The Glycolytic Protein Phosphofructokinase Dynamically Relocalizes into Subcellular Compartments with Liquid-like Properties in vivo

SoRi Jang, Zhao Xuan, Ross C. Lagoy, Louise M. Jawerth, Ian Gonzalez, Milind Singh, Shavanie Prashad, Hee Soo Kim, Avinash Patel, Dirk R. Albrecht, Anthony A. Hyman, Daniel A. Colón-Ramos
doi: https://doi.org/10.1101/636449
SoRi Jang
1Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT, 06536-0812, USA
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Zhao Xuan
1Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT, 06536-0812, USA
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Ross C. Lagoy
2Department of Biomedical Engineering and Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609 USA
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Louise M. Jawerth
3Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, Dresden, Germany
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Ian Gonzalez
1Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT, 06536-0812, USA
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Milind Singh
1Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT, 06536-0812, USA
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Shavanie Prashad
1Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT, 06536-0812, USA
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Hee Soo Kim
1Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT, 06536-0812, USA
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Avinash Patel
3Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, Dresden, Germany
4Dewpoint Therapeutics GmbH, 01307 Dresden, Germany
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Dirk R. Albrecht
2Department of Biomedical Engineering and Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609 USA
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Anthony A. Hyman
3Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, Dresden, Germany
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Daniel A. Colón-Ramos
1Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT, 06536-0812, USA
5Instituto de Neurobiología, Universidad de Puerto Rico, San Juan, Puerto Rico
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  • For correspondence: daniel.colon-ramos@yale.edu
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Abstract

While much is known about the biochemical regulation of glycolytic enzymes, less is understood about how they are organized inside cells. Here we built a hybrid microfluidic-hydrogel device for use in Caenorhabditis elegans to systematically examine and quantify the dynamic subcellular localization of the rate-limiting enzyme of glycolysis, phosphofructokinase-1/PFK-1.1. We determine that endogenous PFK-1.1 localizes to distinct, tissue-specific subcellular compartments in vivo. In neurons, PFK-1.1 is diffusely localized in the cytosol, but capable of dynamically forming phase-separated condensates near synapses in response to energy stress from transient hypoxia. Restoring animals to normoxic conditions results in the dispersion of PFK-1.1 in the cytosol, indicating that PFK-1.1 reversibly organizes into biomolecular condensates in response to cues within the cellular environment. PFK-1.1 condensates exhibit liquid-like properties, including spheroid shapes due to surface tension, fluidity due to deformations, and fast internal molecular rearrangements. Prolonged conditions of energy stress during sustained hypoxia alter the biophysical properties of PFK-1.1 in vivo, affecting its viscosity and mobility within phase-separated condensates. PFK-1.1’s ability to form tetramers is critical for its capacity to form condensates in vivo, and heterologous self-association domain such as cryptochrome 2 (CRY2) is sufficient to constitutively induce the formation of PFK-1.1 condensates. PFK-1.1 condensates do not correspond to stress granules and might represent novel metabolic subcompartments. Our studies indicate that glycolytic protein PFK-1.1 can dynamically compartmentalize in vivo to specific subcellular compartments in response to acute energy stress via multivalency as phase-separated condensates.

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Posted May 13, 2019.
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The Glycolytic Protein Phosphofructokinase Dynamically Relocalizes into Subcellular Compartments with Liquid-like Properties in vivo
SoRi Jang, Zhao Xuan, Ross C. Lagoy, Louise M. Jawerth, Ian Gonzalez, Milind Singh, Shavanie Prashad, Hee Soo Kim, Avinash Patel, Dirk R. Albrecht, Anthony A. Hyman, Daniel A. Colón-Ramos
bioRxiv 636449; doi: https://doi.org/10.1101/636449
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The Glycolytic Protein Phosphofructokinase Dynamically Relocalizes into Subcellular Compartments with Liquid-like Properties in vivo
SoRi Jang, Zhao Xuan, Ross C. Lagoy, Louise M. Jawerth, Ian Gonzalez, Milind Singh, Shavanie Prashad, Hee Soo Kim, Avinash Patel, Dirk R. Albrecht, Anthony A. Hyman, Daniel A. Colón-Ramos
bioRxiv 636449; doi: https://doi.org/10.1101/636449

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