Noa Lipstein

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Accumulated genetic evidence suggests that attenuation of the ratio between cerebral amyloid-β Aβ40 and Aβ42 isoforms is central to familial Alzheimer's disease (FAD) pathogenesis. However, FAD mutations account for only 1-2% of Alzheimer's disease cases, leaving the experience-dependent mechanisms regulating Aβ40/42 an enigma. Here we explored regulation(More)
Short-term synaptic plasticity, the dynamic alteration of synaptic strength during high-frequency activity, is a fundamental characteristic of all synapses. At the calyx of Held, repetitive activity eventually results in short-term synaptic depression, which is in part due to the gradual exhaustion of releasable synaptic vesicles. This is counterbalanced by(More)
Tomosyn is a cytoplasmic protein that was shown to bind to Syntaxin1 and SNAP-25 through an R-SNARE domain, forming a complex that is almost identical in structure to the neuronal SNARE complex. Tomosyn inhibits exocytosis in various cell types and these effects were attributed to direct competition between tomosyn's SNARE domain and Synaptobrevin/VAMP. In(More)
Ca(2+) signalling in neurons through calmodulin (CaM) has a prominent function in regulating synaptic vesicle trafficking, transport, and fusion. Importantly, Ca(2+)-CaM binds a conserved region in the priming proteins Munc13-1 and ubMunc13-2 and thus regulates synaptic neurotransmitter release in neurons in response to residual Ca(2+) signals. We solved(More)
The bioactive surface of scorpion beta-toxins that interact with receptor site-4 at voltage-gated sodium channels is constituted of residues of the conserved betaalphabetabeta core and the C-tail. In an attempt to evaluate the extent by which residues of the toxin core contribute to bioactivity, the anti-insect and anti-mammalian beta-toxins Bj-xtrIT and(More)
Munc13s are presynaptic proteins that mediate synaptic vesicle priming and thereby control the size of the readily releasable pool of vesicles. During high synaptic activity, Munc13-1 and its closely related homolog, ubMunc13-2, bind Ca(2+)/calmodulin, resulting in enhanced priming activity and in changes of short-term synaptic plasticity characteristics.(More)
39 40 Munc13s are presynaptic proteins that mediate synaptic vesicle priming and thereby control 41 the size of the readily releasable pool of vesicles. During high synaptic activity, Munc13-1 42 and its closely related homolog ubMunc13-2 bind Ca 2+ /calmodulin, resulting in enhanced 43 priming activity and in changes of short-term synaptic plasticity(More)
Munc13 proteins are essential regulators of exocytosis. In hippocampal glutamatergic neurons, the genetic deletion of Munc13s results in the complete loss of primed synaptic vesicles (SVs) in direct contact with the presynaptic active zone membrane, and in a total block of neurotransmitter release. Similarly drastic consequences of Munc13 loss are(More)
Scorpion beta and alpha-toxins modify the activation and inactivation of voltage-gated sodium channels. Although the two types of toxin bind at two distinct receptor sites on the same sodium channel, they exhibit synergic effects when coinjected into insects. To clarify the basis of this synergism we examined the mutual effects of alpha and beta toxin(More)
Noa Lipstein, Sabine Schaks, Kalina Dimova,* Stefan Kalkhof,* Christian Ihling, Knut Kölbel, Uri Ashery, JeongSeop Rhee, Nils Brose, Andrea Sinz, and Olaf Jahn Department of Molecular Neurobiology and Proteomics Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany; Department of Pharmaceutical Chemistry & Bioanalytics, Institute of(More)