Patrik Verstreken
Neuronal Communication
VIB Department of Molecular and Developmental Genetics, K.U.Leuven
PhD: Baylor Coll. of Medicine, Houston, USA, '03
Postdoc: Howard Hughes Medical Inst., BCM, Houston, USA, '03-'06
VIB Group leader since 2007
Franqui Hoofddocent, 2009
phone +32 16 33 00 18
address: Gasthuisberg, Herestraat 49, box 602, 6th floor, 3000 Leuven, BELGIUM
Current team members
Group leader: Patrik Verstreken
Postdoctoral scientists: Katarzyna Miskiewicz, Ron Habets, Sven Vilain, Elsa Lauwers, Giovanni Esposito
Ph.D. Students: Ana Clara Fernandes, Dominik Haddad, Jan Slabbaert, Jaroslaw Kasprowicz, Liya Jose, Melissa Vos, Thang Manh Khuong, Valerie Uytterhoeven
Support personnel: Jef Swerts, Onno Schaap, Sabine Kuenen, Tine Pellens
Science, relevant to NERF
How does the nervous system transmit electrical pulses between neurons and how is this process affected in neuronal disease?
We know that neurons talk to one another using small transmitter filled synaptic vesicles that fuse with the neuronal membrane to release neurotransmitters, activating the next cell in line. While considerable progress has been made in identifying proteins present at the synapse, the role of many of them in controlling synaptic vesicle fusion, vesicle reformation at the plasma membrane and trafficking within the nerve terminal remain poorly defined. In the laboratory of neuronal communication we address key aspects of neuronal function by employing a genetic approach that uses fruit flies as a model: we screen for mutations in critical genes and reveal their function by analyzing mutant phenotypes. Illustrating the significance of this approach, several of the genes we identified have been directly linked to deleterious neurological diseases, including Amyotrophic Lateral Sclerosis and Parkinson’s disease. Given the experimental advantages, flies are an ideal system to study vesicle recycling in health and disease. In particular, we combine Drosophila genetics with electrophysiology, electron microscopy and high resolution imaging of synaptic processes. The ability to apply these assays to one single type of synapse is unique and very powerful, allowing us to propose very specific functions for the proteins studied.
Figure: Drosophila neuromuscular junction expressing PLCdPH-GFP (green), a probe that binds the membrane lipid PI(4,5)P2, labeled with pre- and post synaptic markers (anti-HRP: red, and anti-DLG: blue).
Interactions with NERF
While we are focusing on understanding information transfer at single synapses, ultimately, our brain functions by transmitting information in assemblies of millions of neurons and deficient information transfer in specific circuits is thought to lie at the basis of several neurological diseases. We believe that NERF will be able to help us build a bridge between understanding transmission of signals at single synapses to scrutinizing information transfer in neuronal circuits, that direct behavior, memory formation and thought in healthy and diseased brains. Conversely, our understanding of synaptic processes at a cellular level e.g. mitochondrial function, lipid membrane composition or Rab-mediated vesicle trafficking) will allow researchers at NERF to modulate information transfer in synaptic circuits in a medical and functional relevant fashion, eventually allowing the exploration of how these processes affect information transfer in neuronal circuits.
Selected publications
- Verstreken P, Ohyama T, Haueter C, Habets R, Lin Y, Swan L, Ly C, Venken K, De Camilli P, Bellen H
Tweek, an evolutionarily conserved protein, is required for synaptic vesicle recycling
NEURON 63, 203-15, 2009
- Kasprowicz J, Kuenen S, Miskiewicz K, Habets R, Smitz L, Verstreken P
Inactivation of clathrin heavy chain inhibits synaptic recycling but allows bulk membrane uptake J CELL BIOL 182, 1007-16, 2008
- Venken K, Kasprowicz J, Kuenen S, Yan J, Hassan B, Verstreken P
Recombineering-mediated tagging of Drosophila genomic constructs for in vivo localization and acute protein inactivation NUCLEIC ACIDS RES 36, e114, 2008
- Verstreken P, Ly C, Venken K, Koh T, Zhou Y, Bellen H
Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions NEURON 47, 365-78, 2005
- Verstreken P, Kjaerulff O, Lloyd T, Atkinson R, Zhou Y, Meinertzhagen I, Bellen H
Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release CELL 109, 101-12, 2002
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