Solution structure and dynamics of glia maturation factor from Caenorhabditis elegans

Maheshwari, Diva; Shukla, Vaibhav Kumar; Jain, Anupam; Tripathi, Sarita; Kumar, Dinesh; Arora, Ashish

doi:10.1016/j.bbapap.2018.06.007

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…A recent study reported that GMFΒ can be mono-SUMOylated at multiple site by covalent addition of a single SUMO1 protein, fostering the stability and trans-localization of GMFB [ 23 ]. Another important clue is that GMFB is implicated in the regulation of neuronal and glial growth and differentiation [ 25 - 27 ]. Furthermore, GMFB expression is altered in several neurodegenerative diseases, suggesting that GMFB may be a suitable disease biomarker [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

G9a Inhibition Promotes Neuroprotection through GMFB Regulation in Alzheimer’s Disease

et al. 2024

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Epigenetic alterations are a fundamental pathological hallmark of Alzheimer’s disease (AD). Herein, we show the upregulation of G9a and H3K9me2 in the brains of AD patients. Interestingly, treatment with a G9a inhibitor (G9ai) in SAMP8 mice reversed the high levels of H3K9me2 and rescued cognitive decline. A transcriptional profile analysis after G9ai treatment revealed increased gene expression of glia maturation factor β (GMFB) in SAMP8 mice. Besides, a H3K9me2 ChIP-seq analysis after G9a inhibition treatment showed the enrichment of gene promoters associated with neural functions. We observed the induction of neuronal plasticity and a reduction of neuroinflammation after G9ai treatment, and more strikingly, these neuroprotective effects were reverted by the pharmacological inhibition of GMFB in mice and cell cultures; this was also validated by the RNAi approach generating the knockdown of GMFB / Y507A.10 in Caenorhabditis elegans . Importantly, we present evidence that GMFB activity is controlled by G9a-mediated lysine methylation as well as we identified that G9a directly bound GMFB and catalyzed the methylation at lysine (K) 20 and K25 in vitro . Furthermore, we found that the neurodegenerative role of G9a as a GMFB suppressor would mainly rely on methylation of the K25 position of GMFB, and thus G9a pharmacological inhibition removes this methylation promoting neuroprotective effects. Then, our findings confirm an undescribed mechanism by which G9a inhibition acts at two levels, increasing GMFB and regulating its function to promote neuroprotective effects in age-related cognitive decline.

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Section: Introductionmentioning

confidence: 99%

G9a Inhibition Promotes Neuroprotection through GMFB Regulation in Alzheimer’s Disease

et al. 2024

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“…Mammalian cells have two isoforms, GMFβ and GMFγ, both of which colocalize with actin filaments and regulate them [ 4 , 5 ]. The structure of GMF has been solved [ 6 , 7 ], revealing it to be a bona fide member of the actin‐depolymerizing factor homology (ADF‐H) family that includes ADF/cofilin, twinfilin, actin‐binding protein 1 (Abp1)/drebrin, and coactosin. All known ADF‐H proteins bind to either actin and/or Arp2/3 complex and have conserved roles in actin cytoskeleton remodeling [ 8 ].…”

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confidence: 99%

Deletion of gmfA induces keratocyte‐like migration inDictyostelium

et al. 2021

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Glia maturation factor (GMF) has been established as an inactivating factor of the actin‐related protein 2/3 (Arp2/3) complex, which regulates actin assembly. Regulation of actin assembly and reorganization is crucial for various cellular events, such as cell migration, cell division, and development. Here, to examine the roles of ADF‐H domain‐containing protein (also known as glia maturation factor; GmfA), the product of a single GMF homologous gene in Dictyostelium , gmfA‐null cells were generated. They had moderate defects in cell growth and cytokinesis. Interestingly, they showed a keratocyte‐like fan shape with a broader pseudopod, where Arp3 accumulated at higher levels than in wild‐type cells. They migrated with higher persistence, but their velocities were comparable to those of wild‐type cells. The polar pseudopods during cell division were also broader than those in wild‐type cells. However, GmfA did not localize at the pseudopods in migrating cells or the polar pseudopods in dividing cells. Adhesions of mutant cells to the substratum were much stronger than that of wild‐type cells. Although the mutant cells showed chemotaxis comparable to that of wild‐type cells, they formed disconnected streams during the aggregation stage; however, they finally formed normal fruiting bodies. These results suggest that GmfA plays a crucial role in cell migration.

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Analysis of the Clinical Diagnostic Value of GMFB in Cerebral Infarction

Yuan

Zhang

et al. 2020

CPB

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Background: The expression profile and function of GMFB, which mainly expressed in the brain of vertebrates, is still unknown, especially under the condition of nerve injury. Methods and Results: In this study, Immunofluorescence, Western Blot, Immunohistochemistry Staining, TTC staining, Micro-PET and ELISA were applied to analyze the clinical diagnostic value of GMFB in cerebral infarction. The results of Immunofluorescence and Immunohistochemistry Staining showed that GMFB is mainly expressed in the nucleus of nerve cells, and it has the prerequisite for being a chemical marker. The death rate of astrocytes and the concentration of free GMFB protein in the medium increased gradually with the prolongation of hypoxia-ischemia treatment time. Moreover, the levels of GMFB in plasma increased in a rat model of cerebral infarction, which is positively correlated with the degree of infarction. Furthermore, the time dependent increase of GMFB in plasma was confirmed by using clinical samples. The increase of GMFB level appeared at early stage of cerebral infarction (within 24 hours), and sustained for more than one week. Conclusion: In summary, our results provide the evidence that GMFB can be served as a novel indicator for nerve hypoxic-ischemic injury in cell culture, animal model and clinical samples, which play an important role in diagnosis of cerebral infarction.

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Solution structure and dynamics of glia maturation factor from Caenorhabditis elegans

Cited by 3 publications

References 51 publications

G9a Inhibition Promotes Neuroprotection through GMFB Regulation in Alzheimer’s Disease

G9a Inhibition Promotes Neuroprotection through GMFB Regulation in Alzheimer’s Disease

Deletion of gmfA induces keratocyte‐like migration inDictyostelium

Analysis of the Clinical Diagnostic Value of GMFB in Cerebral Infarction

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