Abstract
Metabolite transport across cellular membranes is required for bioenergetic processes and metabolic signaling. The solute carrier family 13 (slc13) transporters mediate transport of the metabolites succinate and citrate and hence are of paramount physiological importance. Nevertheless, the mechanisms of slc13 transport and regulation are poorly understood. Here, a dynamic structural slc13 model suggested that an interfacial helix, H4c, which is common to all slc13s, stabilizes the stationary scaffold domain by anchoring it to the membrane, thereby facilitating movement of the SLC13 catalytic domain. Moreover, we found that intracellular determinants interact with the H4c anchor domain to modulate transport. This dual function is achieved by basic residues that alternately face either the membrane phospholipids or the intracellular milieu. This mechanism was supported by several experimental findings obtained using biochemical methods, electrophysiological measurements in Xenopus oocytes, and fluorescent microscopy of mammalian cells. First, a positively charged and highly conserved H4c residue, Arg108, was indispensable and crucial for metabolite transport. Furthermore, neutralization of other H4c basic residues inhibited slc13...Continue Reading
References
Nov 2, 1987·Nature·M A HedigerE M Wright
Dec 16, 2000·Science·B RoginaS L Helfand
Nov 26, 2002·Biochemical and Biophysical Research Communications·Katsuhisa InoueVadivel Ganapathy
Jun 5, 2003·FEBS Letters·Erik Strandberg, J Antoinette Killian
Aug 14, 2003·Pflügers Archiv : European journal of physiology·Daniel Markovich, Heini Murer
Dec 4, 2003·Biochimica Et Biophysica Acta·Shraddha PrakashMilton H Saier
Mar 11, 2004·The Journal of Biological Chemistry·Nikolay ShcheynikovShmuel Muallem
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jun 28, 2005·Nucleic Acids Research·Johannes SödingAndrei N Lupas
Mar 15, 2006·Nature Genetics·Zhirong JiangPeter S Aronson
Dec 4, 2010·The Journal of Membrane Biology·Eric V SchowDouglas J Tobias
Feb 2, 2011·The Journal of General Physiology·Ehud OhanaShmuel Muallem
Aug 2, 2011·Cell Metabolism·Andreas L BirkenfeldGerald I Shulman
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Oct 23, 2012·Nature·Romina MancussoDa-Neng Wang
Nov 28, 2012·Current Topics in Membranes·Daniel Markovich
Mar 20, 2013·Molecular Aspects of Medicine·Ernest M Wright
Mar 29, 2013·Nature·G M TannahillL A J O'Neill
Jul 9, 2013·Journal of the American Society of Nephrology : JASN·Ehud OhanaShmuel Muallem
Oct 12, 2013·Pflügers Archiv : European journal of physiology·Ana M Pajor
Jun 6, 2015·Cell Research·Beth Kelly, Luke A J O'Neill
Sep 2, 2015·The Journal of Pharmacology and Experimental Therapeutics·Ruud ZwartEmanuele Sher
Sep 20, 2015·Brain : a Journal of Neurology·Katia HardiesUNKNOWN autosomal recessive working group of the EuroEPINOMICS RES Consortium
Feb 2, 2016·Nature Structural & Molecular Biology·Christopher MulliganJoseph A Mindell
May 12, 2016·Nucleic Acids Research·Haim AshkenazyNir Ben-Tal
Apr 25, 2017·Nature Communications·Rongxin NieMin Lu
Nov 13, 2018·Nucleic Acids Research·Thomas D NewportPhillip J Stansfeld
Feb 8, 2019·Journal of the American Society of Nephrology : JASN·Ahlam KhamaysiEhud Ohana
Apr 13, 2019·Nucleic Acids Research·Fábio MadeiraRodrigo Lopez
Citations
Sep 2, 2020·ELife·David B SauerDa-Neng Wang
Oct 21, 2020·The Biochemical Journal·Kei HiguchiVadivel Ganapathy
Oct 23, 2020·The Journal of Biological Chemistry·Connor D D SampsonChristopher Mulligan
Feb 19, 2021·Nature·David B SauerDa-Neng Wang
Jan 18, 2021·The Journal of Biological Chemistry·Connor D D SampsonChristopher Mulligan
Oct 13, 2020·Chemical Reviews·Valeria Jaramillo-MartinezVadivel Ganapathy
Jun 9, 2021·The Biochemical Journal·Valeria Jaramillo-MartinezIna L Urbatsch
Aug 12, 2021·Cell Reports·Moran FremderEhud Ohana