Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1128/MCB.00933-12
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.
Source Titel Molecular and Cellular Biology
Year 2012
Department PROTEOM
Volume 32
Issue 22
Page From 4628
Page To 4641
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.

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 10.1128/MCB.00933-12