Identification of residues/sequences in the human riboflavin transporter-2 that is important for function and cell biology

Nutrition & Metabolism
Veedamali S SubramanianHamid M Said

Abstract

Riboflavin (RF) is essential for normal cellular metabolic activities. Human cells obtain RF from their surroundings via a carrier-mediated process that involves RF transporters -1, -2 & -3 (hRFVT -1, -2 & -3; products of SLC52A1, -A2 and -A3 genes, respectively). Little is known about the structural features of these transporters that are important for their function/cell biology. Our aim in this study was to address these issues for the hRFVT-2, a transporter linked to the neurodegenerative disorder Brown-Vialetto-Van Laere Syndrome (BVVLS). We used comparative protein-structure modelling to predict residues that interact with two amino acids known to be critical for hRFVT-2 function (the clinical mutants L123 and L339), site-directed mutagenesis, and truncation approach in the human-derived brain U87 cell model. First we showed that the defect in the function of the L123 and L339 hRFVT-2 clinical mutants is related to a reduction in protein stability/translation efficiency and to retention of the protein in the ER. Mutating V120 and L121 (residues predicted to interact with L123) and L342 (a residue predicted to interact with L339) also led to a significant inhibition in hRFVT-2 function (with no change in membrane expressio...Continue Reading

References

Aug 1, 1973·The American Journal of Clinical Nutrition·W S RosenthalJ M Cooperman
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Nov 28, 2002·The Journal of Biological Chemistry·Veedamali S SubramanianHamid M Said
Jun 28, 2005·Nucleic Acids Research·Kevin BrysonDavid T Jones
Nov 8, 2005·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·M Verdrengh, A Tarkowski
May 23, 2007·Nucleic Acids Research·Markus Wiederstein, Manfred J Sippl
Jul 18, 2008·American Journal of Physiology. Cell Physiology·Atsushi YonezawaKen-ichi Inui
Jan 6, 2009·Journal of Biochemistry·Syunsuke YamamotoHiroaki Yuasa
Nov 21, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Veedamali S SubramanianHamid M Said
Apr 23, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Veedamali S SubramanianHamid M Said
Nov 22, 2011·Developmental Medicine and Child Neurology·Geetha AnandSandeep Jayawant
Jun 29, 2012·Brain : a Journal of Neurology·Janel O JohnsonAndrew B Singleton
Aug 7, 2012·Journal of Inherited Metabolic Disease·Tobias B HaackHolger Prokisch
Dec 18, 2012·Journal of Medical Genetics·Marianna CiccolellaEnrico Bertini
Nov 21, 2013·Brain : a Journal of Neurology·A Reghan FoleyHenry Houlden
Feb 25, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Sheila Cristina SanchesFernando Silva Ramalho

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Citations

Jun 9, 2016·Journal of Inherited Metabolic Disease·Maria BarileCesare Indiveri
Sep 16, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ram LakhanHamid M Said
Feb 23, 2019·Journal of Inherited Metabolic Disease·Benjamin O'CallaghanHenry Houlden
Jan 23, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Alex Man Lai WuShinya Ito

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Methods Mentioned

BETA
PCR
transfection
Protein Assay
confocal microscopy

Software Mentioned

COR
LI
Graph Pad Prism
Nikon C -

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