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Cited by 5Glycogen Storage Diseases and MyoclonusMetabolism, Diabetes, and CancerGenetics and Neurodevelopmental Disorders

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PURA and GLUT1: Sweet partners for brain health

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Colombo, Rocío B., Maxit, Clarisa, Martinelli, Diego, Anderson, Mel, Masone, Diego, Mayorga, Lía·2024·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
DOI 10.1016/j.bbadis.2024.167261

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Abstract

PURA, also known as Pur-alpha, is an evolutionarily conserved DNA/RNA-binding protein crucial for various cellular processes, including DNA replication, transcriptional regulation, and translational control. Comprising three PUR domains, it engages with nucleic acids and has a role in protein-protein interactions. The manifestation of PURA syndrome, arising from mutations in the PURA gene, presents neurologically with developmental delay, hypotonia, and seizures. In our prior work from 2018, we highlighted the unique case of a PURA patient displaying hypoglycorrhachia, suggesting a potential association with GLUT1 dysfunction in this syndrome. In this current study, we expand the patient cohort with PURA mutations exhibiting hypoglycorrhachia and aim to unravel the molecular basis of this phenomenon. We established an in vitro model in HeLa cells to modulate PURA expression and investigated GLUT1 function and expression. Our findings indicate that PURA levels directly impact glucose uptake through the functioning of GLUT1, without influencing significantly GLUT1 expression. Moreover, our study reveals evidence for a possible physical interaction between PURA and GLUT1, demonstrated by colocalization and co-immunoprecipitation of both proteins. Computational analyses, employing molecular dynamics, further corroborates these findings, demonstrating that PURA:GLUT1 interactions are plausible, and that the stability of the complex is altered when PURA is truncated and/or mutated. In conclusion, our results suggest that PURA plays a pivotal role in driving the function of GLUT1 for glucose uptake, potentially forming a regulatory complex. Additional investigations are warranted to elucidate the precise mechanisms governing this complex and its significance in ensuring proper GLUT1 function.

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Metadata

Authors
Colombo, R. B., Maxit, C., Martinelli, D., Anderson, M., Masone, D., & Mayorga, L.
Affiliations
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
  • Hospital Italiano de Buenos Aires (AR)
  • Bambino Gesù Children's Hospital (IT)
Corresponding author
Mayorga, Lía
ORCID
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher
Elsevier BV
Published
2024-08
Volume
1870
Issue
6
Pages
167261
ISSN
0925-4439 (ISSN-L)
DOI
10.1016/j.bbadis.2024.167261
OpenAlex
W4398146821
Cited by
5
References
4
Citations by year
2026: 2 · 2025: 1 · 2024: 2
FWCI
1.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Agencia Nacional de Promoción Científica y Tecnológica (PIP-0409CO, PICT 2019-00449, PICT 2020-1897)
  • CONICET
  • Nvidia
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Glycogen Storage Diseases and Myoclonus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
PURA, GLUT1, PURA syndrome, hypoglycorrhachia, glucose uptake, protein-protein interaction, brain glucose metabolism, developmental delay, seizures, hypotonia, HeLa cells
MeSH terms
Brain, DNA-Binding Proteins, Female, Glucose, HeLa Cells, Humans, Male, Mutation, Nerve Tissue Proteins, RNA-Binding Proteins, Glucose Transporter Type 1

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CoChat. (2026). Citation check: PURA and GLUT1: Sweet partners for brain health. https://app.cochat.ai/papers/10.1016/j.bbadis.2024.167261
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Colombo, R. B., Maxit, C., Martinelli, D., Anderson, M., Masone, D., & Mayorga, L. (2024). PURA and GLUT1: Sweet partners for brain health. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. https://doi.org/10.1016/j.bbadis.2024.167261