The Glycolytic Enzyme Phosphofructokinase-1 Assembles into Filaments

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

doi:10.1016/j.bpj.2017.11.1268

Cited by 14 publications

(30 citation statements)

References 30 publications

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“…Moreover, the platelet isoform of PFK1 (PFKP) is recruited to the membrane by activated EGFRs and is overexpressed in PDAC (Fig. 1a) [22], whilst the liver isoform of PFK1 (PFKL) has been found to oligomerize to form filaments which were enriched at the plasma membrane [49].…”

Section: Discussionmentioning

confidence: 99%

Metabolic regulation of calcium pumps in pancreatic cancer: role of phosphofructokinase-fructose-bisphosphatase-3 (PFKFB3)

et al. 2020

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Background: High glycolytic rate is a hallmark of cancer (Warburg effect). Glycolytic ATP is required for fuelling plasma membrane calcium ATPases (PMCAs), responsible for extrusion of cytosolic calcium, in pancreatic ductal adenocarcinoma (PDAC). Phosphofructokinase-fructose-bisphosphatase-3 (PFKFB3) is a glycolytic driver that activates key rate-limiting enzyme Phosphofructokinase-1; we investigated whether PFKFB3 is required for PMCA function in PDAC cells. Methods: PDAC cell-lines, MIA PaCa-2, BxPC-3, PANC1 and non-cancerous human pancreatic stellate cells (HPSCs) were used. Cell growth, death and metabolism were assessed using sulforhodamine-B/tetrazolium-based assays, poly-ADPribose-polymerase (PARP1) cleavage and seahorse XF analysis, respectively. ATP was measured using a luciferase-based assay, membrane proteins were isolated using a kit and intracellular calcium concentration and PMCA activity were measured using Fura-2 fluorescence imaging. Results: PFKFB3 was highly expressed in PDAC cells but not HPSCs. In MIA PaCa-2, a pool of PFKFB3 was identified at the plasma membrane. PFKFB3 inhibitor, PFK15, caused reduced cell growth and PMCA activity, leading to calcium overload and apoptosis in PDAC cells. PFK15 reduced glycolysis but had no effect on steady-state ATP concentration in MIA PaCa-2. Conclusions: PFKFB3 is important for maintaining PMCA function in PDAC, independently of cytosolic ATP levels and may be involved in providing a localised ATP supply at the plasma membrane.

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Section: Discussionmentioning

confidence: 99%

Metabolic regulation of calcium pumps in pancreatic cancer: role of phosphofructokinase-fructose-bisphosphatase-3 (PFKFB3)

et al. 2020

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“…Chemotaxis of myeloid cells like other types of cells is also known to require energy in the form of ATP that is produced on demand during migration. ATP is rapidly consumed within the cytosol to fuel the remodeling of the actin cytoskeleton necessary for 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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“…Using both transmission electron microscopy and 90° light scattering, Webb et al (2017) demonstrated that a recombinant liver-specific isoform of PFK1 (liver PFK1; PFKL) forms filaments in vitro. However, filament assembly was not observed in platelet PFK1 (PFKP)- or muscle PFK1–specific isoforms.…”

mentioning

confidence: 99%

“…In addition to identifying PFKL polymerization, Webb et al (2017) examined the filament structure with negative-stain EM and iterative helical real-space reconstruction. They found that PFKL filaments are distinct from other filamentous enzymes.…”

mentioning

confidence: 99%