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| GENTAUR • Belgium : + 32 2 7325688 • France : 01 43250150 • Italy : 02 36006593 • Germany : +49 241 6085 13140 | |
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GABA, Betaine/GABA (BGT-1), and Vesicular GABA Transporter (VGAT) Antibodies
A distinct step in intercellular communication involves termination of synaptic transmission via the removal of neurotransmitters by specialized transporters. The regulated exocytotic release of neurotransmitters in response to neural activity requires storage within intracellular vesicles. In the nervous system, these vesicles are the synaptic vesicles that are derived from the endosomal compartment, whereas in endocrine cells larger secretory granules, such as the chromaffin granules of adrenal medulla, are derived from the trans golgi networks. For classical transmitters that are synthesized in the cytoplasm or appear there after removal from the synapses by plasma membrane reuptake, storage depends upon the active transport into the vesicles. There are 2 classes of transporters: plasma membrane and vesicular. The plasma membrane transporters use an electrochemical gradient of Na+ generated by Na-K+-ATPase and Cl- may also be co-transported. This class of transporters includes the classical neurotransmitters (GABA-Transporter, GAT), norepinephrine (NET), dopamine (DAT), glycine (GLYT), and some other compounds. The other distinct family of transporters are Na/K+-dependent (GLT, EAAC, GLAST, Glutamate/Aspartate transporters). Vesicular transporters catalyze transport and storage of monoamines, serotonin, dopamine, norepinephrine, epinephrine, and histamine. The driving force utilized by the VMAT is the H+ electrochemical gradient generated by a vacuolar ATP-dependent H+ pump located on vesicular plasma membrane. GABA is a major inhibitory neurotransmitter and the GABAergic transmission is terminated by the rapid Na+/Cl-dependent uptake of through GABA transporters. It has been subdivided into neural and glial uptake systems on the basis of pharmacological properties. Recently, molecular cloning studies have identified multiple subtypes of GABA transporters (GAT1, GAT2, GAT3; and betaine GABA transporter (BGT-1). There is ~50% homology between various GABA transporter subtypes. GABA transporters are predicted to contain 12 potential transmembrane domains. The NH2 and COOH-termini are predicted to be intracellular. Two of the high affinity (Km~10 uM) rat GABA transporters (GAT2 and GAT3/GAT-B) share higher amino acid identity (68% and 65%, respectively) with the kidney betaine transporter than with GAT-1 (52% AA identity). GAT1 and GAT3 have been detected in various parts of the brain while GAT2 is found in many tissues. It appears that GAT1 and GAT3 are involved in distinct GABAergic transmission while GAT2 may be important in non-neural functions. Most recently, a rat homologue of C. elegans GABA transporter gene unc-47 termed VGAT (vesicular GABA transporter) has been cloned. The rat VGAT gene encodes a protein of 525 aa with 38% identity and 56% similarity to unc-47. VGAT is predicted to contain ten transmembrane domains. It has a large (132 aa) hydrophilic N-terminus. Both N and C-termini are predicted to be cytoplasmic. Rat VGAT is expressed in GABAergic neurons and colocalizes with synaptic vesicles. ADI has produced highly specific
rabbit-antibodies to rat GAT1, GAT2, GAT3, VGAT and BGT-1 using peptide
sequences specific to each protein. These antibodies should be useful in
studying specific transporters.
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