Proteolytic maturation of α<sub>2</sub>δ controls the probability of synaptic vesicular release.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29916807.
- Also identified by DOI 10.7554/eLife.37507 and PMC identifier 6029843.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Auxiliary α<sub>2</sub>δ subunits are important proteins for trafficking of voltage-gated calcium channels (Ca<sub>V</sub>) at the active zones of synapses. We have previously shown that the post-translational proteolytic cleavage of α<sub>2</sub>δ is essential for their modulatory effects on the trafficking of N-type (Ca<sub>V</sub>2.2) calcium channels (Kadurin et al., 2016). We extend these results here by showing that the probability of presynaptic vesicular release is reduced when an uncleaved α<sub>2</sub>δ is expressed in rat neurons and that this inhibitory effect is reversed when cleavage of α<sub>2</sub>δ is restored. We also show that asynchronous release is influenced by the maturation of α<sub>2</sub>δ-1, highlighting the role of Ca<sub>V</sub> channels in this component of vesicular release. We present additional evidence that Ca<sub>V</sub>2.2 co-immunoprecipitates preferentially with cleaved wild-type α<sub>2</sub>δ. Our data indicate that the proteolytic maturation increases the association of α<sub>2</sub>δ-1 with Ca<sub>V</sub> channel complex and is essential for its function on synaptic release.
Medical subject headings
- Calcium Channels, N-Type
- Neurons
- Protein Subunits
- Synaptic Vesicles