Targeting Tools: GAT1-SAP

GAT-1 is a sodium-coupled neurotransmitter transporter responsible for moving g-aminobutyric acid (GABA) across cell membranes. GABA is the predominant inhibitory neurotransmitter in the mammalian central nervous system. GAT-1 is widely distributed in both the central and peripheral nervous systems. GAT-1 and GABA are present in numerous neuronal pathways, some of which are implicated in epilepsy, sleep disorders, neuropathic pain, and attention deficit disorders.

We have constructed a conjugate between an antibody to an extracellular domain of GAT-1 and saporin, the ribosome- inactivating protein. This construct, GAT1-SAP (Cat. #IT-32) has been used to specifically remove GABAergic neurons of the anterior bed nucleus of the stria terminalis (1) and the medial septum and diagonal band of rats (2). Figure 1 shows the specificity of the targeted toxin, with parvalbumin-positive neurons being drastically reduced, while most cholinergic neurons are spared.

Coming soon is our vesicular GABA transporter-saporin construct to increase the ability to eliminate specific populations of GABAergic neurons.

References

1. Radley JJ, Gosselink KL, Sawchenko PE. (2009) A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response. J Neurosci 29(22):7330-40.

2. Pang KC, Jiao X, Sinha S, Beck KD, Servatius RJ. (2010) Damage of GABAergic neurons in the medial septum impairs spatial working memory and extinction of active avoidance: Effects on proactive interference. Hippocampus. Epub, May 17.


GAT1-SAP, Cat. #IT-32
available in these sizes: 25 micrograms, 100 micrograms, and 250 micrograms

Kit includes the following controls in equal amounts:
Saporin, Cat. #PR-01
GAT-1 Rabbit Polyclonal, Cat. #AB-N37
Rabbit IgG-SAP, Cat. #IT-35


Immunocytochemistry following sham surgery (top row) or administration of GAT1-SAP (bottom row, 325 ng/μl) into the medial septum-diagonal band of Broca (MSDB). Staining of parvalbumin-immunoreactive neurons in the MSDB was dramatically reduced following GAT1-SAP administration (left). Parvalbumin- ir neurons in the MSDB are GABAergic septohippocampal neurons. In contrast to parvalbumin-ir neurons, neither cholinergic neurons (ChAT-ir, middle) nor calbindin-ir neurons (right) were altered following GAT1-SAP application in the MSDB. Scale bar – 200 μm. Figure provided by KCH Pang et al. (2008) Targeting Trends 9(1).
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