{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:24:35Z","timestamp":1772252675926,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,17]],"date-time":"2020-02-17T00:00:00Z","timestamp":1581897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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)-1\u03b1, which activates the transcription of target genes to orchestrate a cellular response to low oxygen. One of the genes induced by HIF-1\u03b1 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-1\u03b1 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-1\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms21041341","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T04:06:01Z","timestamp":1582085161000},"page":"1341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Rho\/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates Hif-1\u03b1 and Glut-1 Expression and Glucose Uptake in the Brain"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3456-3672","authenticated-orcid":false,"given":"Jaewoo","family":"Hong","sequence":"first","affiliation":[{"name":"Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurim","family":"Kim","sequence":"additional","affiliation":[{"name":"Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"},{"name":"Department of Biology, University of Maryland, College Park, MD 20742, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudhirkumar","family":"Yanpallewar","sequence":"additional","affiliation":[{"name":"Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. Charles","family":"Lin","sequence":"additional","affiliation":[{"name":"Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E836","DOI":"10.1152\/ajpendo.00496.2009","article-title":"Will the original glucose transporter isoform please stand up!","volume":"297","author":"Carruthers","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/ng0298-188","article-title":"GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier","volume":"18","author":"Seidner","year":"1998","journal-title":"Nat. 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