scholarly journals The RhoA Guanine Nucleotide Exchange Factor, LARG, Mediates ICAM-1–Dependent Mechanotransduction in Endothelial Cells To Stimulate Transendothelial Migration

2014 ◽  
Vol 192 (7) ◽  
pp. 3390-3398 ◽  
Author(s):  
Elizabeth C. Lessey-Morillon ◽  
Lukas D. Osborne ◽  
Elizabeth Monaghan-Benson ◽  
Christophe Guilluy ◽  
E. Timothy O’Brien ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Guanine Nucleotide Exchange Factor ◽  
Transendothelial Migration ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Exchange Factor ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor

scholarly journals The Rho/Rac guanine nucleotide exchange factor Vav1 regulates HIF-1α and GLUT-1 expression and glucose uptake in the brain

2019 ◽  
Author(s):  
Jaewoo Hong ◽  
Yurim Kim ◽  
Sudhirkumar Yanpallewar ◽  
P. Charles Lin
Keyword(s):  
Endothelial Cells ◽  
Glucose Uptake ◽  
Guanine Nucleotide Exchange Factor ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Glut 1 ◽  
Exchange Factor ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
The Brain

AbstractVav1 is a Rho/Rac 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-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-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. They 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.

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