RGD Reference Report - Balance of calcineurin Aa and CDK5 activities sets release probability at nerve terminals. - Rat Genome Database

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Balance of calcineurin Aa and CDK5 activities sets release probability at nerve terminals.

Authors: Kim, Sung Hyun  Ryan, Timothy A 
Citation: Kim SH and Ryan TA, J Neurosci. 2013 May 22;33(21):8937-50. doi: 10.1523/JNEUROSCI.4288-12.2013.
RGD ID: 13792535
Pubmed: PMID:23699505   (View Abstract at PubMed)
PMCID: PMC3808255   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.4288-12.2013   (Journal Full-text)

The control of neurotransmitter release at nerve terminals is of profound importance for neurological function and provides a powerful control system in neural networks. We show that the balance of enzymatic activities of the α isoform of the phosphatase calcineurin (CNAα) and the kinase cyclin-dependent kinase 5 (CDK5) has a dramatic influence over single action potential (AP)-driven exocytosis at nerve terminals. Acute or chronic loss of these enzymatic activities results in a sevenfold impact on single AP-driven exocytosis. We demonstrate that this control is mediated almost entirely through Cav2.2 (N-type) voltage-gated calcium channels as blocking these channels with a peptide toxin eliminates modulation by these enzymes. We found that a fraction of nerve terminals are kept in a presynaptically silent state with no measurable Ca(2+) influx driven by single AP stimuli attributable to the balance of CNAα and CDK5 activities because blockade of either CNAα or CDK5 activity changes the proportion of presynaptically silent nerve terminals. Thus, CNAα and CDK5 enzymatic activities are key determinants of release probability.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
presynapse located_inIMP 13792535PMID:23699505ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Cdk5  (cyclin-dependent kinase 5)


Additional Information