Lina Malinauskaité: Neurotransmitter: Sodium Symporters: Caught in the Act!

The neurotransmitter: sodium symporters in the neurons. Communication between neurons is mediated by the release of molecules called neurotransmitters (blue dots) from first neuron and sensed by receptors on the surface of the second (purple sphere). The signal is ended by active reuptake of these neurotransmitters by a family of proteins called neurotransmitter: sodium symporters (NSS), which are driven using the large concentration difference of sodium (orange dots) between the outside and the inside of the cell.

15 November 2013 by Lisbeth Heilesen

Neurons are the functional unit of the brain. Communication between neurons is through electrical signals and chemical messengers called neurotransmitters. A family of proteins called the neurotransmitter:sodium symporters (NSS) are critical in terminating this communication (see Figure). Defects in the NSS proteins are related to psychiatric and neurological disorders and these proteins are targets for antidepressants and addictive drugs like cocaine and amphetamine. Insight into how these NSS proteins work has come from crystal structures of a bacterial homolog captured in various states. However, key questions on how the driving force is converted at a molecular level to promote release, and how the protein later returns in an empty state to become ready for another transport cycle have remained unanswered.

During her PhD studies, Lina Malinauskait? investigated an alternative bacterial homolog of the NSS family and has obtained two new crystal structures that represent previously unknown snapshots of the transport cycle. The first is of a closed state with everything bound showing how sodium can next be released to the intracellular side. The second is again a closed, but now empty state explaining how the transporter protein can return to another transport cycle. These results give very important insights to the transport mechanism of this protein family.

Time: Friday 15 November 2013 at 13.00
Place: Eduard Biermann Aud. (1252-204), The Lakeside Lecture Theatres
Title of dissertation: Structural and Functional Studies of the Neurotransmitter:Sodium Symporter Family: Insight into the Transport Mechanism
Contact information: Lina Malinauskaité, e-mail: linam@mb.au.dk
Members of the assessment committee:
Associate Professor Dirk Jan Slotboom, Faculty of Mathematics and Natural Sciences, University of Groningen
Associate Professor Osman Mirza, Department of Drug Design and Pharmacology, University of Copenhagen
Associate Professor Ditlev E. Brodersen (chair), Department of Molecular Biology and Genetics, Aarhus University
Main supervisor:
Professor Poul Nissen, DANDRITE, Department of Molecular Biology and Genetics, Aarhus University
Language: The PhD dissertation will be defended in English.

The defence is public.
The dissertation is available for reading at the Graduate School of Science and Technology/GSST, Ny Munkegade 120, building 1521, room 112, 8000 Aarhus C.