Author:
Wierda Keimpe D. B.,Toft-Bertelsen Trine L.,Gøtzsche Casper R.,Pedersen Ellis,Korshunova Irina,Nielsen Janne,Bang Marie Louise,Kønig Andreas B.,Owczarek Sylwia,Gjørlund Michelle D.,Schupp Melanie,Bock Elisabeth,Sørensen Jakob B.
Abstract
AbstractClassically, neurexins are thought to mediate synaptic connections through trans interactions with a number of different postsynaptic partners. Neurexins are cleaved by metalloproteases in an activity-dependent manner, releasing the soluble extracellular domain. Here, we report that in both immature (before synaptogenesis) and mature (after synaptogenesis) hippocampal neurons, the soluble neurexin-1β ectodomain triggers acute Ca2+-influx at the dendritic/postsynaptic side. In both cases, neuroligin-1 expression was required. In immature neurons, calcium influx required N-type calcium channels and stimulated dendritic outgrowth and neuronal survival. In mature glutamatergic neurons the neurexin-1β ectodomain stimulated calcium influx through NMDA-receptors, which increased presynaptic release probability. In contrast, prolonged exposure to the ectodomain led to inhibition of synaptic transmission. This secondary inhibition was activity- and neuroligin-1 dependent and caused by a reduction in the readily-releasable pool of vesicles. A synthetic peptide modeled after the neurexin-1β:neuroligin-1 interaction site reproduced the cellular effects of the neurexin-1β ectodomain. Collectively, our findings demonstrate that the soluble neurexin ectodomain stimulates growth of neurons and exerts acute and chronic effects on trans-synaptic signaling involved in setting synaptic strength.
Funder
FP7 People: Marie-Curie Actions
FP7 Ideas: European Research Council
European Cooperation in Science and Technology
Lundbeckfonden
Independent Research Fund Denmark
Novo Nordisk Fonden
Publisher
Springer Science and Business Media LLC
Cited by
7 articles.
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