xCT, encoded by the gene SLC7A11, is a member of the heterodimeric amino acid transporter family. Proteins within this family are linked to one another via a disulphide bond to form heterodimers consisting of one light subunit and one heavy subunit (1). These heterodimers facilitate the transport of amino acids across cell membranes. The light subunit xCT dimerises with the heavy subunit 4F2hc and the role of the xCT-4F2hc heterodimer, also known as system Xc-, is to couple the release of one molecule of intracellular glutamate to the uptake of one molecule of extracellular cystine (2).
Immunohistochemistry: xCT Antibody
Glutamate is the primary excitatory neurotransmitter in the mammalian brain. It is stored in vesicles at synapses, from which its release is triggered during nerve impulses. Non-vesicular glutamate is released during cystine-glutamate exchange; this method of glutamate release is less well understood, but the glutamate is thought to activate non-synaptic receptors and to play several key roles in controlling synaptic function. The uptake of cystine is a vital function that is served by this exchange; following uptake the cystine is converted to cysteine, an amino acid that is found only at very low levels in plasma and cerebrospinal fluid. The cysteine is subsequently transported in to neurons, where it supports glutathione production. Glutathione is a critical antioxidant which prevents damage to cellular components caused by reactive oxygen species.
xCT and glutamatergic dysfunction have been implicated in a range of disorders of the central nervous system including schizophrenia, drug addiction and depression (3). In addition, research is ongoing to establish whether there may also be a link between glutamatergic dysfunction and neurodegenerative conditions such as Alzheimer’s disease.
Shih, et. al. have used xCT antibodies in Western blotting to demonstrate the distribution of xCT in distinct regions of both embryonic and adult rat brain (4). Liu, et. al. have used xCT antibodies to evaluate levels of the protein in various tumour cell lines; xCT is implicated in chemotherapeutic resistance in some cancers, where a significant increase in cystine uptake is associated with improved tumour cell survival. (5)
Novus Biologicals offers various xCT reagents for your research needs including:
Written by Emma Easthope
