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Patrik Verstreken
Neuronal Communication
VIB Department of Molecular and Developmental Genetics, K.U.Leuven
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PhD: Baylor Coll. of Medicine, Houston, USA, '03
Postdoc: Howard Hughes Medical Inst., BCM, Houston, USA, '03-'06
VIB Group leader since 2007 |
e-mail
phone +32 16 33 00 18
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Current team members
Group leader: Patrik Verstreken
Postdoctoral scientists: Elsa Lauwers, Giovanni Esposito, Katarzyna Miskiewicz, Ron Habets, Sven Vilain
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, Lindsey Robyns, Onno Schaap, Sabine Kuenen, Tine Pellens
Keywords
synapse - neurotransmitter release and endocytosis - Drosophila - mitochondria - imaging and electrophysiology
Science
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. Fusion and endocytosis of vesicles are regulated by numerous proteins and lipids, and in the laboratory of neuronal communication we address key aspects of neuronal function. To study these processes in vivo, we employ a genetic approach using fruit flies as a model: we screen for mutations in critical genes and reveal their function by analyzing mutant phenotypes. Given the experimental advantages, flies are an ideal system to study vesicle recycling. In particular, we combine Drosophila genetics with electrophysiology, electron microscopy, immunohistochemistry, calcium imaging, live dye uptake and release studies, and pharmacological inhibition 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.
As a general strategy, in the lab we employ genetic screens to identify and characterize components affecting synaptic function. In one such approach we are screening the Drosophila genome by feeding flies chemical mutagens and we use simple electrophysiological assays to isolate genes that impact the synapse. Several of the genes we identified in this screen are now under investigation and our studies have already revealed novel and exciting aspects of vesicle recycling and synaptic function. In a second approach we are testing genes implicated in neurological disease for defects in synaptic function or development. Flies are well suited to study the mechanisms underlying synaptic function in humans since all key synaptic proteins identified also exist in flies, and they show on average 75% protein similarity to their mammalian counterparts. The ability to combine human disease phenotypes with genetic screening strategies using simple assays is relatively unique and will provide new insights into common processes that underlie neurological disease progression and synaptic transmission. Already now we note a convergence of our two screen approaches where our chemical mutagenesis screen identifies mutations in neurological disease genes, and conversely, our neurological disease gene screen points to novel players in synaptic function. Hence, we believe that our screen approaches are complementary to one another and when combined, will shed new light on mechanisms of synaptic communication in healthy and diseased neurons.
Link to Group’s website for more details. (http://verstreken.vib.be/)
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
Search Publications
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