Contact

Dr. Tanja Maritzen
phone +49 30 94793 - 214 (office)/ -368 (lab)
maritzen(at)fmp-berlin.de

Maritzen Lab Research

Endocytic sorting at the synapse

Sustained neurotransmission relies on the local recycling of synaptic vesicles, which requires the efficient retrieval of transmembrane synaptic vesicle proteins from the presynaptic membrane after vesicle fusion. Consequently, neurons depend on fast and reliable sorting processes to regenerate synaptic vesicles of the right protein composition for sustained neurotransmission. Our work aims at dissecting the molecular mechanisms underlying the high-fidelity sorting of synaptic vesicle proteins.

In collaboration with the group of Volker Haucke we have demonstrated that efficient neurotransmission relies on the use of dedicated endocytic adaptors to internalize crucial synaptic vesicle proteins. A prominent example is the importance of the endocytic adaptor AP180 for the retrieval of the vesicular SNARE protein Synaptobrevin2 which is crucial for synaptic vesicle fusion. Even though Synaptobrevin2 is a very abundant protein on synaptic vesicles, its partial missorting to the plasma membrane upon loss of AP180 has dramatic consequences for the organism. AP180 deficient mice display reduced excitatory and inhibitory neurotransmission. In fact, the inhibitory neurotransmission is even more affected. This is likely due to the fact that inhibitory neurons are often tonically active and therefore have a higher demand of synaptic vesicle recycling. Since inhibitory neurotransmission is the brake that in a healthy brain prevents excitatory neurons from over-excitation, its decrease in AP180 deficient mice leads to seizures which cause premature death. Thus high-fidelity retrieval of synaptobrevin2 by AP180 is indeed crucial for brain function and survival (Kononenko et al. Neuron, 2015). Currently, we are interested in the physiological role of the AP180 related protein CALM which has been linked to Alzheimer´s disease.

 

Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
+4930 94793 - 109 (Fax)
info(at)fmp-berlin.de

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