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RSS FeedsIJMS, Vol. 21, Pages 1341: The Rho/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates Hif-1? and Glut-1 Expression and Glucose Uptake in the Brain (International Journal of Molecular Sciences)

 
 

18 february 2020 03:02:53

 
IJMS, Vol. 21, Pages 1341: The Rho/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates Hif-1? and Glut-1 Expression and Glucose Uptake in the Brain (International Journal of Molecular Sciences)
 


Vav1 is a Rho/Rac (Ras-related C3 botulinum toxin substrate) guanine nucleotide exchange factor expressed in hematopoietic and endothelial cells that are involved in a wide range of cellular functions. It is also stabilized under hypoxic conditions when it regulates the accumulation of the transcription factor HIF (Hypoxia Inducible Factor)-1α, which activates the transcription of target genes to orchestrate a cellular response to low oxygen. One of the genes induced by HIF-1α is GLUT (Glucose Transporter)-1, which is the major glucose transporter expressed in vessels that supply energy to the brain. Here, we identify a role for Vav1 in providing glucose to the brain. We found that Vav1 deficiency downregulates HIF-1α and GLUT-1 levels in endothelial cells, including blood-brain barrier cells. This downregulation of GLUT-1, in turn, reduced glucose uptake to endothelial cells both in vitro and in vivo, and reduced glucose levels in the brain. Furthermore, endothelial cell-specific Vav1 knock-out in mice, which caused glucose uptake deficiency, also led to a learning delay in fear conditioning experiments. Our results suggest that Vav1 promotes learning by activating HIF-1α and GLUT-1 and thereby distributing glucose to the brain. We further demonstrate the importance of glucose transport by endothelial cells in brain functioning and reveal a potential new axis for targeting GLUT-1 deficiency syndromes and other related brain diseases.


 
171 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 21, Pages 1337: Combined Analysis of the Metabolome and Transcriptome Identified Candidate Genes Involved in Phenolic Acid Biosynthesis in the Leaves of Cyclocarya paliurus (International Journal of Molecular Sciences)
IJMS, Vol. 21, Pages 1340: Role of Signal Transduction Pathways and Transcription Factors in Cartilage and Joint Diseases (International Journal of Molecular Sciences)
 
 
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