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Title (Primary) Non-conserved Ca2+/calmodulin binding sites in Munc13s differentially control synaptic short-term plasticity
Author Lipstein, N.; Schaks, S.; Dimova, K.; Kalkhof, S.; Ihling, C.; Kolbel, K.; Ashery, U.; Rhee, J.; Brose, N.; Sinz, A.; Jahn, O.;
Journal Molecular and Cellular Biology
Year 2012
Department PROTEOM;
Volume 32
Issue 22
Language englisch;
Abstract

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 Ca2+/calmodulin, resulting in enhanced priming activity and in changes of short-term synaptic plasticity characteristics. Here, we studied whether bMunc13-2 and Munc13-3, two remote isoforms of Munc13-1 with a neuronal subtype-specific expression pattern, mediate synaptic vesicle priming and regulate short-term synaptic plasticity in a Ca2+/calmodulin-dependent manner. We identified a single functional Ca2+/calmodulin binding site in these isoforms, and provide structural evidence that all Munc13s employ a common mode of interaction with calmodulin, despite the lack of sequence homology between their Ca2+/calmodulin binding sites. Electrophysiological analysis showed that, during high frequency activity, Ca2+/calmodulin binding positively regulates the priming activity of bMunc13-2 and Munc13-3, resulting in an increase in the size of the readily releasable pool of vesicles and subsequently in strong short-term synaptic enhancement of neurotransmission. We conclude that Ca2+/calmodulin-dependent regulation of priming activity is structurally and functionally conserved in all Munc13 proteins, and that the composition of Munc13 isoforms in a neuron differentially controls its short-term synaptic plasticity characteristics.

ID 12925
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=12925
Lipstein, N., Schaks, S., Dimova, K., Kalkhof, S., Ihling, C., Kolbel, K., Ashery, U., Rhee, J., Brose, N., Sinz, A., Jahn, O. (2012):
Non-conserved Ca2+/calmodulin binding sites in Munc13s differentially control synaptic short-term plasticity
Mol. Cell. Biol. 32 (22), 4628 - 4641