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Extracellular filaments of Pyrobaculum calidifontis

ABSTRACT:

SUBMITTER: Fengbin Wang

PROVIDER: EMPIAR-11699 | biostudies-other |

REPOSITORIES: biostudies-other

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Extracellular cytochrome nanowires appear to be ubiquitous in prokaryotes.

Baquero Diana P DP Cvirkaite-Krupovic Virginija V Hu Shengen Shawn SS Fields Jessie Lynda JL Liu Xing X Rensing Christopher C Egelman Edward H EH Krupovic Mart M Wang Fengbin F

Cell 20230607 13

Electrically conductive appendages from the anaerobic bacterium Geobacter sulfurreducens, recently identified as extracellular cytochrome nanowires (ECNs), have received wide attention due to numerous potential applications. However, whether other organisms employ similar ECNs for electron transfer remains unknown. Here, using cryoelectron microscopy, we describe the atomic structures of two ECNs from two major orders of hyperthermophilic archaea present in deep-sea hydrothermal vents and terres ...[more]

PMID: 37290436

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IMPDH2 filaments protect from neurodegeneration in AMPD2 deficiency

Project description:Metabolic dysregulation is one of the most common causes of pediatric neurodegenerative disorders. However, how the disruption of ubiquitous and essential metabolic pathways predominantly affect neural tissue remains unclear. Here we use a mouse model of AMPD2 deficiency to study cellular and molecular mechanisms that lead to selective neuronal vulnerability to purine metabolism imbalance. We show that AMPD deficiency in mice primarily leads to hippocampal dentate gyrus degeneration despite causing a generalized reduction of brain GTP levels. Remarkably, we uncover that neurodegeneration resistant regions of the hippocampus accumulate micron sized filaments of IMPDH2, the rate limiting enzyme in GTP synthesis. In contrast, IMPDH2 filaments are barely detectable in the dentate gyrus, which show a progressively neuroinflammation and neurodegeneration. Furthermore, using a human AMPD2 neural cell culture model, we show that blocking IMPDH2 polymerization with a dominant negative IMPDH2 variant impairs AMPD2 deficient neural progenitor growth. Together, our findings suggest that IMPDH2 polymerization prevents detrimental GTP deprivation caused by AMPD2 deficiency, providing resistance to neurodegeneration. This data opens the possibility of exploring the involvement of IMPDH2 assembly as a therapeutic intervention for neurodegeneration.

2024-01-16 | GSE253045 | GEO

Artificial Intracellular Filaments.