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The neurotransporter group

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The Group studies how transporter proteins (in normal and diseased brains of different ages) modulate the extracellular spatiotemporal concentration profiles of excitatory (glutamate and aspartate) and inhibitory (GABA and glycine) transmitter amino acids. The transporters studied are those able to transport aspartate, GABA, glutamate, glycine and monoamines across brain plasma membranes. These include the glutamate (EAAT1-5), GABA (GAT1-4), glycine (GLYT1-2), dopamine (DAT) and dicarboxylate (SDCT2) transporters as well as the glutamate-cystine exchanger and their anchoring and regulatory proteins.

Challenges

The human genome contains about 300 different transporter protein genes. Many of the encoded transporters, including those for glutamate, are subject to sophisticated dynamic regulation, and are also ion channels in addition to being transporters. Thus, the transporters appear to have more refined functions than just being pumps, but these functions are poorly understood. The overall aim of the Group is to determine the roles of the individual transporter subtypes in order to better understand normal physiology and disease, and to uncover new therapeutic opportunities. Disturbed control of extracellular glutamate appears to be an important factor, directly or indirectly, in all neurological disorders as well as in drug abuse and major psychiatric disorders (e.g. schizophrenia), as a consequence of the abundance of glutamate, the ubiquitous presence of glutamate receptors, and the interplay between glutamate, oxidation and energy metabolism (for review see: Danbolt, 2001: Prog. Neurobiol).

Projects

  • Production of suitable tools (including antibodies) and model systems (including gene modified animals)
  • Determination of transporter distributions and densities around select synapses in normal adult brains and how these parameters change during development, ageing, drug use and disease
  • Computer modelling of transmitter release, diffusion, removal and receptor activation
  • Transporter protein purification, reconstitution and crystallisation

Group leader

Professor Niels Christian Danbolt

Department of Anatomy & CMBN
University of Oslo
PO Box 1105 Blindern
NO-0317 Oslo
Norway

Tel: +47 22851260 or +47 22851041
Fax: +47 22851278
E-mail: n.c.danbolt@medisin.uio.no

The distribution of glutamate transporter proteins.

Centre for Molecular Biology and Neuroscience (CMBN)
PO Box 1105 Blindern, NO-0317 Oslo, Norway. Tel: +47 22851528. Fax: +47 22851488