The amino acid transporter asc-1 is not involved in cystinuria

Abstract

The lack of expression of asc-1 in the proximal tubule indicates that it plays no role in the bulk of renal reabsorption of amino acids. No mutations causing cystinuria have been found in SLC7A10. The facilitated diffusion mode of transport and the expression in distal nephron suggest a role for asc-1 in osmotic adaptation.

Identification and Functional Characterization of a Novel Low Affinity Aromatic-preferring Amino Acid Transporter (arpAT)

“…Transport of 50 M L-alanine was 123.9 Ϯ 18.3 pmol/mg of protein/min in untransfected HeLa cells (n ϭ 7 independent transfections with 4 replicas each), 148.1 Ϯ 23.5 in 4F2hc-transfected cells (n ϭ 3; 9 g of DNA/cell dish), 115.3 Ϯ 20.4 in rBAT-transfected cells (n ϭ 3; 9 g of DNA/cell dish), 211 Ϯ 15.4 in arpAT-transfected cells (n ϭ 5; 18 g of DNA/cell dish), 316.4 Ϯ 44.7 in 4F2hc and arpAT co-transfected cells (n ϭ 5; 9 g of each DNA/cell dish), and 420.3 Ϯ 18 in rBAT and arpAT co-transfected cells (n ϭ 7; 9 g of each DNA/cell dish). The results indicate that arpAT binds both 4F2hc and rBAT and suggests that, when transfected alone, arpAT may recruit the endogenous 4F2hc protein, as shown for other LSHATs (17).…”

“…Cystine transport through xCT in nonepithelial cell lines is a rate-limiting step in glutathione biosynthesis, contributing to redox control (16). Human asc1 (and probably also mouse asc2) may participate in osmotic adaptation at the distal nephron (10,17), and y ϩ LAT2 could release dibasic amino acids in non-epithelial tissues (18). Apical system b 0,ϩ mediates most of the apical (re)absorption of cystine and part of the (re)absorption of dibasic amino acids, acting in concert with the heterodimers y ϩ LAT1-4F2hc and LAT2-4F2hc (19), which mediate the net efflux of dibasic amino acids and cysteine across the basolateral membrane to the blood, respectively (20 -22).…”

Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia

“…Because asc-1 (SLC7A10) is localized next to the non-type I cystinuria gene SLC7A9 (b 0,ϩ AT, see sect. IIIC) on chromosome 19, its role in amino acid absorption was investigated further (274). The transporter is expressed in the loop of Henle, the distal tubule, and collecting ducts.…”

Absorption, Transport, and Retention

“…The combination of asc-1 (SLC7A10) and 4F2 mediates the transport of small neutral amino acids, beta-alanine, and some D amino acids at the basolateral membrane of the thin limbs of Henle's loop, distal tubules, and collecting ducts (Pineda et al, 2004). These transporters can exchange a cationic amino acid for a neutral amino acid plus a sodium ion.…”