Affiliation:
1. Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA
Abstract
The role of the sodium citrate transporter (NaCT) SLC13A5 is multifaceted and context-dependent. While aberrant dysfunction leads to neonatal epilepsy, its therapeutic inhibition protects against metabolic disease. Notably, insights regarding the cellular and molecular mechanisms underlying these phenomena are limited due to the intricacy and complexity of the latent human physiology, which is poorly captured by existing animal models. This review explores innovative technologies aimed at bridging such a knowledge gap. First, I provide an overview of SLC13A5 variants in the context of human disease and the specific cell types where the expression of the transporter has been observed. Next, I discuss current technologies for generating patient-specific induced pluripotent stem cells (iPSCs) and their inherent advantages and limitations, followed by a summary of the methods for differentiating iPSCs into neurons, hepatocytes, and organoids. Finally, I explore the relevance of these cellular models as platforms for delving into the intricate molecular and cellular mechanisms underlying SLC13A5-related disorders.
Reference175 articles.
1. Mutations in SLC13A5 Cause Autosomal-Recessive Epileptic Encephalopathy with Seizure Onset in the First Days of Life;Thevenon;Am. J. Hum. Genet.,2014
2. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia;Hardies;Brain,2015
3. Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action;Inoue;Biochem. J.,2003
4. Human Na+ -coupled citrate transporter: Primary structure, genomic organization, and transport function;Inoue;Biochem. Biophys. Res. Commun.,2002
5. Structure, Function, and Expression Pattern of a Novel Sodium-coupled Citrate Transporter (NaCT) Cloned from Mammalian Brain;Inoue;J. Biol. Chem.,2002