Sørensen Lab – University of Copenhagen

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CNS > Research > Section for Molecular and Cellular Neuroscience > Sørensen Lab

Sørensen Lab

Interests: My group has expertise in studying the molecular and cellular mechanisms of neurotransmitter release in chemical synapses and in neuroendocrine cells.

The key goals of the laboratory include

i) identifying the components and detailed mode-of-action of the machinery for neurotransmitter release, including the molecular differences between synchronous, asynchronous and spontaneous release phases, which are all necessary to keep balanced network activity,

ii) understanding how the release mechanisms are regulated physiologically to ensure exocytotic and presynaptic robustness and plasticity,

iii) determine how these mechanisms are affected by disease (e.g. epilepsy, ADHD and Intellectual Disability, which are known to be correlated to mutations in the release machinery), and

iv) identify the link between neurotransmitter release defects and neuronal death.

Currently, our focus is on neuroendocrine cells and hippocampal glutamatergic and GABAergic neurons kept in auto-innervating (autaptic) cultures on astrocyte islands. We use advanced electrophysiological (patch-clamp) and optical methods (incl. superresolution microscopy and uncaging of lipids and Ca2+), combined with cell culture and viral transduction methods for expression and knock-down. Our work has identified key regulatory steps in the assembly of the release machinery, which can form the basis for pharmacological intervention.

We have identified the stoichiometry of the SNARE complex needed for fast release. Recently, we have also identified novel components of the vesicle biosynthetic pathways. Current efforts also involve the generation of 3D mathematical models of the presynapse to understand the origins of short-term synaptic plasticity, synaptic robustness and the abrupt appearance of disease at a mutation threshold.

Key publications last 10 years

  • Schupp M., ..., and Sørensen J.B. Interactions between SNAP-25 and synaptotagmin-1 are involved in vesicle priming, clamping spontaneous and eliciting evoked neurotransmission. J. Neurosci. (2016) 36:11865-11880.
  • Schotten S., ..., Sørensen J.B.*, Verhage M.*, and Cornelisse L.N.*. Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate. *Equal contributions. Elife (2015) 4:e05531.
  • Walter A.M., ..., and Sørensen J.B. The SNARE protein vti1a functions in dense-core vesicle biogenesis. EMBO J (2014) 33,1681-1697.
  • Walter A.M., Groffen A.J., Sørensen J.B., and Verhage M. Multiple Ca(2+) sensors in secretion: teammates, competitors or autocrats? Trends Neurosci. (2011) 34:487-497.
  • Mohrmann R., ..., Sørensen J.B. Fast vesicle fusion in living cells requires at least three SNARE-complexes. Science (2010) 330, 502-505.
  • Weber J.P., ..., Sørensen J.B. Opposing roles of two sub-domains of the SNARE-complex in neurotransmission. EMBO J. (2010) 29, 2477-2490.
  • Walter A.M., ..., Sørensen J.B. Synaptobrevin N-terminally bound to SNAP-25:syntaxin defines the primed vesicle state in regulated exocytosis. J. Cell Biol. (2010) 188, 401-413.
  • De Wit H., ..., Sørensen J.B.*, and Verhage M.* Synaptotagmin docks secretory vesicles to SNAP-25:syntaxin dimers. Cell (2009) 138, 935-946. (*Shared last-authorship).

Overall publication metrics: Number of peer reviewed papers: 60; H-index: 33; i10-index: 47 (Google scholar).

Jakob Balslev Sørensen

Section and lab leader: Professor Jakob Balslev Sørensen