Neurexins cluster Ca2+ channels within the presynaptic active zone
Fujun Luo1, Alessandra Sclip1, Man Jiang1
1Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University Medical School, Stanford, CA, USA.
The EMBO Journal
|March 6, 2020
Summary
Neurexins are crucial for fast neurotransmission by linking calcium channels to release sites at the synapse. This study shows neurexin deletion impairs this coupling, suppressing neurotransmitter release.
Area of Science:
- Neuroscience
- Cell Biology
- Synaptic Plasticity
Background:
- Neurons utilize highly organized presynaptic and postsynaptic nanomachines for ultrafast neurotransmission.
- Synaptic adhesion molecules, like neurexins, are essential for aligning these nanomachines.
- The precise role of neurexins in controlling presynaptic active zone assembly via trans-synaptic interactions is not fully understood.
Purpose of the Study:
- To investigate the function of neurexin adhesion molecules in the assembly and function of presynaptic active zones.
- To determine how neurexins influence neurotransmitter release at the calyx of Held synapse.
Main Methods:
- Conditional deletion of all three neurexin adhesion molecules from presynaptic neurons in the mouse calyx of Held.
- Biophysical analyses of synaptic properties, including calcium currents and neurotransmitter release.
- Assessment of calcium channel and BK potassium channel function.
Main Results:
- Pan-neurexin deletion did not affect synapse development or the basic release machinery.
- Fast neurotransmitter release was dramatically impaired following neurexin deletion.
- Neurexin deletion impaired the coupling of calcium influx to exocytosis.
- Function of calcium-activated BK potassium channels was reduced.
Conclusions:
- Neurexins are essential for coupling presynaptic calcium channels to release sites at the calyx synapse.
- This coupling is critical for efficient fast neurotransmitter release.
- Neurexins play a key role in regulating synaptic transmission speed and efficacy.
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