# SLC45A4 encodes a peroxisomal putrescine transporter that promotes GABA de novo synthesis

## TL;DR

The study identifies SLC45A4 as a transporter that helps produce GABA in peroxisomes by moving putrescine.

## Contribution

The novel contribution is identifying SLC45A4 as a peroxisomal putrescine transporter involved in GABA synthesis.

## Key findings

- SLC45A4 expression correlates with GABA levels in cells.
- SLC45A4 transports putrescine in peroxisomes to promote GABA synthesis via the AOP pathway.
- The study reveals a new biochemical role for an orphan transporter.

## Abstract

Solute carriers (SLC) are membrane proteins that facilitate the transportation of ions and metabolites across either the plasma membrane or the membrane of intracellular organelles. With more than 450 human genes annotated as SLCs, many of them are still orphan transporters without known biochemical functions. We develop a metabolomic-transcriptomic association analysis, and we find that the expression of SLC45A4 has a strong positive correlation with the cellular level of γ-aminobutyric acid (GABA). Using mass spectrometry and the stable isotope tracing approach, we demonstrate that SLC45A4 promotes GABA de novo synthesis through the Arginine/Ornithine/Putrescine (AOP) pathway. SLC45A4 functions as a putrescine transporter localized to the peroxisome membrane to facilitate GABA production. Taken together, our results reveal a biochemical mechanism where SLC45A4 controls GABA production.

Many SLC transporters are still orphan transporters. Here, the authors developed a transcriptomic-metabolomic association analysis, which revealed the role of SLC45A4. They found that SLC45A4 is a peroxisomal transporter for putrescine, promoting GABA de novo synthesis in non-neuronal cells.