Details

Start in MolTag:  27.06.2022

Title of the project: Diffusion Barriers and spatiotemporal organization of the serotonin transporter in the plasma membrane in relation to its oligomeric state

Research topic:

The serotonin transporter (SERT) belongs to the SLC6 transporter family and mediates the re-uptake of serotonin from the synaptic cleft. It has been shown via single-molecule microscopy that SERT forms stable higher-order oligomers of differing stoichiometry at the plasma membrane that are kinetically trapped in this state by phosphatidylinositol-4,5-bisphosphate (PIP2) binding. Controlled SERT oligomerization might provide a cellular mechanism for differentially regulating its confinement to plasma membrane domains. While oligomers are impeded by diffusional barriers, monomers are sufficiently small to escape. According to this hypothesis, reduced PIP2 availability triggers the dissociation of the quaternary complex and thereby enables SERT escape from membrane domains.

In my thesis, I will study the spatiotemporal organization of SERT via single molecule tracking and single molecule localization microscopy. The goal is to determine the role of SERT oligomerization in the regulation of SERT distribution, on its own but also in combination with hitherto unknown interacting proteins.