Shupliakov Laboratory


Oleg Shupliakov

Phone: 08-524 878 49
Organizational unit: Department of Neuroscience (Neuro), C4

Research focus

Communication between cellular compartments, cell surface, and neighboring cells occurs to a large extent via small membrane vesicles filled with different cargo. We study the molecular and biophysical mechanisms underlying vesicle trafficking and targeting in living cells and in particular in neurons.

Our current interest is in scaffolding molecules, which may simultaneously interact with several effector proteins and signaling molecules. To address our goals we use several experimental and genetic model systems such as giant reticular spinal axon in lamprey, Drosophila neuromuscular junction, mammalian cell cultures, and in vitro molecular assays in combination with molecular biology, genetics, cellular imaging techniques, and intracellular recordings.

Our recent studies show that molecular scaffolds are involved in coordination and targeting of effector molecules in endocytosis, vesicle fusion, and vesicle trafficking. Mutations in these proteins are implicated in neurodegenerative diseases and cancer. We believe that our studies will pave the way for identification of therapeutic targets for treatments of these disorders.

Schematic illustration of the role of scaffolding molecules in synaptic vesicle (SV) clustering during neurotransmitter release in interneuronal synapses.  Two systems of protein-protein interactions organize SVs in the pool at rest. Synapsin (red) controls short-distance interaction between SVs, while the scaffolding complex that includes Dap160/Intersectin as well as other endocytic proteins is interspacing vesicles. During synaptic activity phosphorylated synapsin disperses from SV, while the scaffolding complex follows SV membrane in fusion and promotes its recycling.

After disassembly of clathrin-coated vesicles Dap160/Intersectin presumably becomes phosphorylated, comes into interaction with phosphorylated synapsin and the scaffolding complex targets it to vesicles. After or during translocation back to the active zone proteins become dephosphorylated and interaction between synapsin and Dap160/intersectin reduces. Other endocytic proteins, such as dynamin come into interaction with Dap160/Intersectin. Synapsin interlinks vesicles while Dap160/intersectin together with other endocytic proteins form a scaffolding complex that interspaces vesicles thus closing the cycle (Winther et al., 2015).

Selected publications

An Endocytic Scaffolding Protein together with Synapsin Regulates Synaptic Vesicle Clustering in the Drosophila Neuromuscular Junction.
Winther Ã, Vorontsova O, Rees K, Näreoja T, Sopova E, Jiao W, et al
J. Neurosci. 2015 Nov;35(44):14756-70

Membrane Charge Directs the Outcome of F-BAR Domain Lipid Binding and Autoregulation.
Kelley C, Messelaar E, Eskin T, Wang S, Song K, Vishnia K, et al
Cell Rep 2015 Dec;13(11):2597-609

Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease.
Laguna A, Schintu N, Nobre A, Alvarsson A, Volakakis N, Jacobsen J, et al
Nat. Neurosci. 2015 Jun;18(6):826-35

The dynamin-binding domains of Dap160/intersectin affect bulk membrane retrieval in synapses.
Winther Ã, Jiao W, Vorontsova O, Rees K, Koh T, Sopova E, et al
J. Cell. Sci. 2013 Feb;126(Pt 4):1021-31

Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition.
von Kleist L, Stahlschmidt W, Bulut H, Gromova K, Puchkov D, Robertson M, et al
Cell 2011 Aug;146(3):471-84

Group members

Gianvito Arpino - PhD student

Tuomas Näreoja - Postdoc

Oleg Shupliakov - Professor

Elena Sopova - Research assistant

Anna Sundborger - Postdoc

Olga Vorontsova - Research engineer

Ã…sa Winther - Senior researcher