Fernández, E. et al. The structural and functional units of heteromeric amino acid transporters. The heavy subunit rBAT dictates oligomerization of the heteromeric amino acid transporters. J. Biol. Chem. 281, 26552-26561

Department of Cell Biology, University of Barcelona, Barcino, Catalonia, Spain
Journal of Biological Chemistry (Impact Factor: 4.57). 10/2006; 281(36):26552-61. DOI: 10.1074/jbc.M604049200
Source: PubMed


Heteromeric amino acid transporters are composed of a catalytic light subunit and a heavy subunit linked by a disulfide bridge. We analyzed the structural and functional units of systems b0,+ and xC-, formed by the heterodimers b0,+ AT-rBAT and xCT-4F2hc, respectively. Blue Native gel electrophoresis, cross-linking, and fluorescence resonance energy transfer in vivo indicate that system b0,+ is a heterotetramer [b0,+ AT-rBAT]2, whereas xCT-4F2hc seems not to stably or efficiently oligomerize. However, substitution of the heavy subunit 4F2hc for rBAT was sufficient to form a heterotetrameric [xCT-rBAT]2 structure. The functional expression of concatamers of two light subunits (which differ only in their sensitivity to inactivation by a sulfhydryl reagent) suggests that a single heterodimer is the functional unit of systems b0,+ and xC-.

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    • "These proteins are essential for the transport of organic molecules, especially amino acids. Together with slc7a9, slc3a1 represents the rBAT/b0,+AT transporter that is primarily localized in the epithelial cells of the proximal tubules [32]. It is essential for the renal reabsorption of the amino acid cystin [33] and mutations in slc3a1 or slc7a9 interfere with the function of the rBAT/b0,+AT transporter. "
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    • "The 4F2hc subunit is a type II membrane glycoprotein commonly expressed in cells since it acts as a subunit for various amino acid transporters (Chillaron et al., 2001; Verrey et al., 2004). It may be noted that the 4F2hc subunit of x À c can be replaced by rBAT, another HSHAT, with retention of x À c activity (Wang et al., 2003; Fernandez et al., 2006). "
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