AI Article Synopsis
- Heterozygous mutations in PRRT2 are linked to disorders like epilepsy, kinesigenic dyskinesia, and migraines, primarily due to reduced PRRT2 expression.
- PRRT2 is found at presynaptic terminals, and its silencing causes fewer synapses and more docked synaptic vesicles, disrupting normal neurotransmitter release.
- PRRT2 is crucial for the final stages of neurotransmitter release by interacting with key synaptic proteins and influencing calcium sensitivity and release probability.
Article Abstract
Heterozygous mutations in proline-rich transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders, including epilepsy, kinesigenic dyskinesia, and migraine. Most of the mutations lead to impaired PRRT2 expression, suggesting that loss of PRRT2 function may contribute to pathogenesis. We show that PRRT2 is enriched in presynaptic terminals and that its silencing decreases the number of synapses and increases the number of docked synaptic vesicles at rest. PRRT2-silenced neurons exhibit a severe impairment of synchronous release, attributable to a sharp decrease in release probability and Ca(2+) sensitivity and associated with a marked increase of the asynchronous/synchronous release ratio. PRRT2 interacts with the synaptic proteins SNAP-25 and synaptotagmin 1/2. The results indicate that PRRT2 is intimately connected with the Ca(2+)-sensing machinery and that it plays an important role in the final steps of neurotransmitter release.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826441 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2016.03.005 | DOI Listing |
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