The glycolytic enzyme phosphofructokinase-1 assembles into filaments

Webb, Bradley A.; Dosey, Anne M.; Wittmann, Torsten; Kollman, Justin M.; Barber, Diane L.

doi:10.1083/jcb.201701084

Cited by 84 publications

(118 citation statements)

References 47 publications

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“…We observed that PFK-1.1 (F674K) proteins were incapable of forming condensates upon transient hypoxia, and remained diffusely localized (Figures 7B-7C and S6E). Our findings are consistent with tetramer formation being necessary for the oligomerization of PFK (Webb et al, 2017), and provide support for multivalent interactions being necessary for the formation of PFK-1.1 condensates.…”

Section: Multivalent Interactions Underlie Pfk-11 Condensate Formationsupporting

confidence: 86%

“…Similar observations in mammalian tissue culture cells also demonstrated that glycolytic enzymes co-localize into clusters (Kohnhorst et al, 2017). A human isoform of phosphofructokinase (PFK) was recently shown to assemble into tetramers that oligomerize into higher-ordered filamentous structures in vitro (Webb et al, 2017). In the same study, the ability for the PFK to oligomerize in vitro was proposed to underpin its ability to dynamically compartmentalize in tissue culture cells in response to specific metabolites.…”

Section: Introductionmentioning

confidence: 69%

“…Liquid-liquid phase separation can be induced via multivalent protein-protein and protein-RNA interactions (Alberti et al, 2019;Banani et al, 2017;Elbaum-Garfinkle et al, 2015;Langdon et al, 2018;Li et al, 2012;Nott et al, 2015;Smith et al, 2016;Wang et al, 2018;Zhang et al, 2015). PFK exists as a homotetramer capable of self-associating into higher-order structures (Webb et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Instead, PFK forms tetramers through hydrophobic interfaces that facilitate multivalent interactions (Webb et al, 2015). Furthermore, PFK tetramers have dihedral symmetry and can associate into higher-order oligomeric structures (Garcia-Seisdedos et al, 2017;Sola-Penna et al, 2010;Webb et al, 2017).…”

Section: Multivalent Interactions Underlie Pfk-11 Condensate Formationmentioning

confidence: 99%

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

Jang

Zhao

Lagoy

et al. 2019

Preprint

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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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Section: Multivalent Interactions Underlie Pfk-11 Condensate Formationsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Multivalent Interactions Underlie Pfk-11 Condensate Formationmentioning

confidence: 99%

See 2 more Smart Citations

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

Jang

Zhao

Lagoy

et al. 2019

Preprint

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“…ATP is rapidly consumed within the cytosol to fuel the remodeling of the actin cytoskeleton necessary for cell migration. 23,34 There is evidence to suggest that nutrient availability in the microenvironment can indirectly influence myeloid cell migration.…”

Section: Metabolic Regulation Of Myeloid Cell Migrationmentioning

confidence: 99%

Metabolic regulation of leukocyte motility and migration

Marelli‐Berg

Jangani

2018

Journal of Leukocyte Biology

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Dynamic reorganization of the cytoskeleton is essential for numerous cellular processes including leukocyte migration. This process presents a substantial bioenergetic challenge to migrating cells as actin polymerization is dependent on ATP hydrolysis. Hence, migrating cells must increase ATP production to meet the increased metabolic demands of cytoskeletal reorganization. Despite this long-standing evidence, the metabolic regulation of leukocyte motility and trafficking has only recently begun to be investigated. In this review, we will summarize current knowledge of the crosstalk between cell metabolism and the cytoskeleton in leukocytes, and discuss the concept that leukocyte metabolism may reprogram in response to migratory stimuli and the different environmental cues received during recirculation ultimately regulating leukocyte motility and migration.

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Infinite Ansammlungen gefalteter Proteine im Kontext von Evolution, Krankheiten und Proteinentwicklung

2019

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Mutationen und Veränderungen in der Umgebung eines Proteins sind bekannt dafür, potenziell Fehlfaltungen und Aggregation wie Amyloidbildung zu verursachen. Derartige Einflüsse können allerdings auch neue Interaktionen bewirken, die zur Polymerisation gefalteter Proteine führen. Im Unterschied zur Aggregation können solche Vorgänge aber auch ohne Fehlfaltungen ablaufen. Um diesen Unterschied hervorzuheben, bezeichnen wir sie als Agglomeration. Dieser Begriff umfasst die amorphe Zusammenlagerung gefalteter Proteine wie auch deren ein‐, zwei‐ und dreidimensionale Polymerisation. Wir möchten auf die bemerkenswerte Fähigkeit symmetrischer Homooligomere hinweisen, sogar infolge einzelner Oberflächenmutationen zu agglomerieren. Wir erörtern des Weiteren die ambivalente Natur dieser Eigenschaft: Durch Agglomeration entstandene anomale Ansammlungen können einerseits zum Entstehen von Krankheiten beitragen, sind aber andererseits auch für die zelluläre Anpassung verantwortlich und können zudem für das zielgerichtete Design neuer Biomaterialien genutzt werden.

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The glycolytic enzyme phosphofructokinase-1 assembles into filaments

Cited by 84 publications

References 47 publications

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

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

Metabolic regulation of leukocyte motility and migration

Infinite Ansammlungen gefalteter Proteine im Kontext von Evolution, Krankheiten und Proteinentwicklung

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