Tissue‐specific deletion of mouse basolateral uniporter LAT4 (Slc43a2) reveals its crucial role in small intestine and kidney amino acid transport

Abstract

LAT4 is a broadly expressed uniporter selective for essential branched chain amino acids, methionine and phenylalanine, which are involved in epithelial transport. r Its global deletion leads to an early malnutrition-like phenotype and death within 10 days after birth. r Here, we tested the impact of deleting LAT4 selectively in the mouse intestine. This affected slightly the absorption of amino acids (AAs) and delayed gastrointestinal motility; however, it had no major phenotypic effect, even when combined with aromatic AA uniporter TAT1 knockout (KO). r Conversely, kidney tubule-selective deletion of LAT4 led to a substantial aminoaciduria that strongly increased under a high protein diet. Combining a partial tubular LAT4 deletion with TAT1 KO implicated their synergistic action on AA reabsorption. r These results show that LAT4 plays an important role for kidney AA reabsorption, but that its functional role in intestinal AA absorption is largely dispensable.

Dynamic cellular changes in acute kidney injury caused by different ischemia time

“…The genes in PT-3 were significantly enriched in monocarboxylic acid metabolic process and response to protein misfolding ( Figure 4 D). Of interest, PT-1 highly expressed neutral amino acid transporters Slc6a19 , Slc43a2 and Slc7a8 , 17 , 18 , 19 and the expression levels of Slc6a19 , Slc43a2 and Slc7a8 were downregulated in PT-1 during AKI progression ( Figure 4 E). As shown in Figure 4 F, Slc6a19 was colocalized with Slc5a2 on the luminal membrane of proximal tubule.…”

“…The cells expressing Slc6a19 near glomerulus were greatly decreased in Group AKI-30 ( Figure 4 F), which may also affect the reabsorption of sodium ions and homeostasis. Slc6a19, Slc7a8 and Slc43a2 are neutral amino acid transporters, 17 , 18 , 19 , 37 regulating the transport and reabsorption of amino acids such as leucine, isoleucine, and valine, as well as methionine and phenylalanine. 38 Mutations in the gene encoding Slc6a19 were reported to cause human Hartnup disorder, an autosomal recessive defect resulting from impaired of renal and gastrointestinal neutral amino acid transport.…”

Proteomic Analysis of the Intestinal Resistance to Thyroid Hormone Mouse Model With Thyroid Hormone Receptor Alpha Mutations

“…For amino acid metabolism, the large neutral amino acid transporter small subunit 4 (Lat4) was significantly downregulated. Lat4 is mainly present in the crypts and plays an important role in amino acid (AA) transport across the cellular barrier in intestinal development ( 48 – 50 ). We speculate that these proteins associated with the absorption of nutrients could be associated with the impaired postnatal development of the Thra E403X/E403X mice.…”

Analysis of L-leucine amino acid transporter species activity and gene expression by human blood brain barrier hCMEC/D3 model reveal potential LAT1, LAT4, B0AT2 and y+LAT1 functional cooperation

“… 31 On the other hand, the conditional knockout of intestinal LAT4 resulted in no major phenotype indicating the lethal defect is not necessarily solely due to an intestinal LAT4 deficiency. 35 …”

“…31 On the other hand, the conditional knockout of intestinal LAT4 resulted in no major phenotype indicating the lethal defect is not necessarily solely due to an intestinal LAT4 deficiency. 35 B 0 AT2 has been proposed as a candidate for the unidentified Na þ -dep transporter for LNAAs, whose activity has been detected in abluminal BBB endothelium membranes. 36,37 High B 0 AT2 expression has been demonstrated in cerebral cortex, hippocampus, cerebellum, midbrain, and olfactory bulb, localized to BBB astrocytes and neurons.…”