The solute carrier (SLC) family is the largest group of transporters that include hundreds of members. SLC36A4 (PAT4), is a member of the SLC36/proton dependent amino acid transporter (PAT) family, which belongs to the β-group of amino acid transporters. SLC36A4 is a high-affinity transporter of neutral amino acids like proline and tryptophan but it has a lower affinity for alanine and glycine. It is the most recently characterized transporter in the SLC36 family. Studies have reported the ubiquitous expression of this protein in various tissues as well as in several cancer cell lines, although the detailed expression pattern has not been established. The pH dependence is distinct from other PAT transporters, with transport being maximal at pH 7.4 and reduced at pH 5.5 and pH 8.4. The gene for SLC36A4 is located on human chromosome 11q21.
|Basic Information of SLC36A4|
|Protein Name||Proton-coupled amino acid transporter 4|
|Gene Name||SLC36A4, PAT4|
|Aliases||Solute carrier family 36 member 4|
|Organism||Homo sapiens (Human)|
SLC36A4 appears to function by facilitated diffusion in an electroneutral, Na+-independent manner with a relatively high affinity for substrates proline and tryptophan. Moreover, based on genetic knockdown and overexpression in cultured human cells, several studies have indicated that it has also been associated with the function of mTORC1 on the Golgi, a complex in the mammalian target of rapamycin (mTOR) pathway. In addition, SLC36A4 may take on a more prominent function in some cancers. For instance, the high SLC36A4 expression is associated with reduced relapse-free survival after colorectal cancer surgery.
Fig.1 SLC36A4 responds to amino acids to regulate mTORC1 function on the Golgi apparatus. (Fan, 2018)
Using in situ hybridization, immunohistological analysis, RT-PCR study, and phylogenetic analysis, this study investigated the expression profile of PAT4. The results showed that PAT4 has an abundant expression in excitatory and inhibitory neurons, and in the plasma membrane of epithelial cells.
This article studied the role of PAT4 in colorectal cancer. The results showed that PAT4 upregulation was associated with cancer progression. By using an inducible PAT4 shRNA knockdown in HCT116 colorectal cancer cells, the authors found that PAT4 responded to glutamine and serine to drive rapamycin-resistant, mTORC1-mediated cell proliferation. There was also evidence showed that PAT4 interacted with Rab1A and mTORC1 on the Golgi.
This study reported small GTPase Rab12 as a new type of autophagic regulator that controlled the degradation of the amino acid transporter PAT4, which might be a new mechanism of regulation of mTORC1 signaling and autophagy.
This study characterized the hPAT4 expressed in Xenopus laevis oocytes. The results also showed that this protein was a high-affinity/low-capacity non-proton-coupled amino acid transporter.
This study provided evidence that PAT4 regulated the amino acid pool in the lysosomes of the retinal pigmented epithelium (RPE) using Cryba1 (gene encoding βA3/A1-crystallin) knockout mice.
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