Neuronal membrane trafficking – Oleg Shupliakov group

We study the molecular and biophysical mechanisms underlying and regulating vesicle trafficking in neurons and in particular in their axons and presynaptic nerve terminals. Our current interest is in the molecular mechanisms, which link the synaptic vesicle cycle with the onset of neurodegenerative diseases and primarily under conditions that lead to α-synuclein-related pathologies observed in Parkinson’s disease, as well as in several diseases referred to as synucleinopathies.

Research focus

Liquid-liquid phase separation in cells has emerged as a common principle for the organization of membrane-less compartments. In nerve terminals in the central nervous system, liquid-liquid phase separation has been implicated in the organization or assembly of several functional compartments. We are aiming at characterizing the signaling mechanisms that regulate the liquid-liquid phase transitions in the synaptic vesicle cycle, mitochondrial functions, and degradation pathways at nerve terminals to clarify how do they become affected at the early stages of neurodegenerative diseases and which molecular steps lead to protein aggregate formation. To address our goals we use several model systems such as giant reticular spinal axon in lamprey, Drosophila neuromuscular junction, and mammalian neurons, in combination with molecular biology, genetics, cellular imaging techniques, and intracellular recordings.

We believe that our experiments will pave the way for the identification of therapeutic targets for treatments of neurodegenerative disorders.

Publications

Selected publications

Funding

Our studies are supported by Vetenskapsrådet (Swedish Research Council), Hjärnfonden and Parkinsonfonden.