Achievements

1. Danbolt was the first, in collaboration with BI Kanner in Israel, to purify a glutamate transporter protein using reconstitution of transport activity to monitor the purification process (Danbolt et al., 1990). Antibodies to the purified protein was use to localize (Danbolt et al., 1992) and clone a glutamate transporter,  which turned out to define a new gene family (Nature 360:464 1992).

2. The group was first to discover that neurons modulate glutamate transporter expression in astrocytes (Levy et al., 1995). The transporters are also regulated by several other mechanisms (J. Biol. Chem. 268:27313 1992; J. Biol. Chem. 271:5976 1996; J.Neurochem. 69:2612 1997; TIPS 19:3281998; Nat Neurosci. 2:427 1999). A disease related functionally impaired mutant has been identified (J. Biol. Chem. 276: 576).

3. The group has studied the localization of neurotransmitter transporters using light and electron microscopic immunocytochemistry (e.g. Lehre et al., 1995; Dehnes et al., 1998) and has provided the data on the densities of transporter molecules (Lehre and Danbolt, 1998; for review see: Danbolt, 2001).  The EAAT2-subtype represents about 1 % of total adult hippocampus protein. The transporters are form oligomers consisting of non-covalently attached subunits (Haugeto et al., 1996).

4. The existence of glutamate uptake in excitatory terminals was verified by uptake and immunogold quantification of the slowly metabolized analogue D-aspartate and shown to be due to the EAAT2 subtype (Furness et al., 2008).

5. This work has shown that the transporters play complex roles in the normal functioning of the nervous system as well as in neurological disorders (for review see: Danbolt 2001). The main interest in recent years has been to obtain quantitative data in order to perform computer simulations. What are all of these transporters doing together? Precise quantitative data, however, requires rigorous specificity controls and access to transgenic animals (Holmseth 2005, 2006, Holmseth et al., 2012a and 2012b). 

6. The betaine-GABA transporter (BGT1) line was developed to address test the hypothesis that BGT1 plays a role in seizure control. Surprisingly, BGT1 does not a play a role in the brain and only plays a minor role in the kidney. The main function of BGT1 is in the liver (Lehre et al., 2011; Zhou et al., 2012) illustrating the importance of using transgenic animals.

7. Deletion of the gene encoding the GABA transporter 2 (GAT2, slc6a13) in mice revealed that this transporter is mostly expressed in the liver where it serves as a taurine transporter (Zhou et al., 2012 ). It is also expressed in kidneys. In the brain, it is found in some blood vessels and in the leptomeninges at the brain surface. Thus, neither GAT2 nor BGT1 are important in controlling the action of transmitter GABA in the brain. 

8. The logistics of this research activity has become complex, and that lead to an interest in databasing to improve the efficiency of the research process. Due to increasing numbers of methods, reagents, electronic files and higher mobility of both people and materials it is hard to keep track. The traditional notebooks are inadequate, and the group has introduced an electronic notebooks system from Science Linker AS based on novel principles of database design suggested by KP Lehre.

Published Apr. 18, 2011 2:05 PM - Last modified Dec. 18, 2012 4:40 PM