Rescuing folding-deficient SLC6 transporters and GPCRs by pharmacochaperoning
Austria (AMSA) - University of Vienna, Vienna
Institute for Pharmacology
Michael Freissmuth, Univ.-Prof.
Michael Freissmuth, Univ.-Prof.
4 weeks
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
No No No No No No Yes Yes Yes No No No
Type of Research Project
- Basic science
What is the background of the project?
Background: We work on transporters of the SLC6 (solute carrier 6 gene) family, which includes the transporters for neurotransmitters (serotonin, dopamine, GABA (gamma-aminobutyric acid), glycine etc.) and osmolytes and related compounds (e.g. taurine, betaine, creatine) and G protein-coupled receptors. The aim is to understand their trafficking from their site of synthesis, i.e. the endoplasmic reticulum, to their final destination (e.g. the presynaptic specialization). Folding-deficient versions of these proteins arise form point mutations; they are the underlying cause of diseases (e.g. mutations in the creatine transporter and in dopamine transporter give rise to mental retardation and infantile dystonia/Parkinson's disease, respectively).
What is the aim of the project?
The goal is to identify compounds, which restore function by overcoming the folding defect ("pharmacochaperones")
What techniques and methods are used?
Cell culture, cellular transfections, site-direcetd mutagenesis, confocal microscopy, radioligand binding and substrate uptake assays; immunoblotting and immunoprecipitation
What is the role of the student?
What are the tasks expected to be accomplished by the student?
Carry out cellular transfections; measure substrate uptake (in a radiochemical assay); immunoblot for core- and mature glycosylated forms of the protein; do immunorpecipitations to identify associated proteins; fluorescence microscopy to identiy the cellular copmartn´ment where the protein resides
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
experience in lab work would be an asset
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts:
- Medical students
- Graduated students (less than 6 months)
- Pre-Medical students from the American-British system
- Students in biomedical fields
- Montgomery TR; Sucic S; El-Kasaby A; Kudlacek O; Sarker S; Sitte HH; Marin P; Freissmuth M (2011) The serotonin transporter is an exclusive client of the coat protein complex II (COPII) component SEC24C. J Biol Chem 286:16482-16490
- Sucic S; Koban F; El-Kasaby A; Kudlacek O; Stockner T; Sitte HH; Freissmuth M (2013) Switching the clientele: a lysine residing in the C-terminus of the serotonin transporter specifies its preference for the COPII component SEC24C. J Biol Chem. 288:5330-5341 doi: 10.1074/jbc.M112.408237.
- Steinkellner T; Sucic S; Koban F; Sch