Related Experiment Videos
Control of a novel adenylyl cyclase by calcineurin
J M Paterson1, S M Smith, A J Harmar
1MRC Brain Metabolism Unit, University of Edinburgh, Scotland, UK.
Abstract:
The molecular complex formed by the immunosuppressant FK506 and the immunophilin protein FKBP12 potently inhibits the Ca2+/calmodulin-activated protein phosphatase calcineurin. This mechanism appears to be common to all types of cell, implying that fundamental physiological modes of calcineurin regulation are exploited by immunosuppressants. The present paper describes a novel adenylyl cyclase regulated by calcineurin that contains an FKBP12-like domain and may thus constitute a physiologically relevant calcineurin docking site mimicked by immunosuppressant-immunophilin complexes. The enzyme messenger RNA is particularly enriched in the cerebral cortex, striatum and hippocampus, where it is localized to neuronal perikarya, indicative of an important role in neuronal function.
Insights
The immunosuppressant FK506 and FKBP12 protein complex inhibits calcineurin. A novel calcineurin-regulated adenylyl cyclase with an FKBP12-like domain may be a physiological target for these drugs.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- The immunosuppressant FK506 forms a complex with FKBP12, inhibiting calcineurin, a Ca2+/calmodulin-activated protein phosphatase.
- This inhibition mechanism is conserved across cell types, suggesting exploitation of fundamental calcineurin regulation by immunosuppressants.
Purpose of the Study:
- To identify novel physiological targets of calcineurin.
- To investigate the role of calcineurin in neuronal function.
Main Methods:
- Identification and characterization of a novel adenylyl cyclase.
- Analysis of enzyme messenger RNA distribution and localization in the brain.
Main Results:
- A novel adenylyl cyclase regulated by calcineurin was discovered.
- This enzyme possesses an FKBP12-like domain, suggesting it could be a physiological calcineurin binding site.
- The enzyme's mRNA is highly expressed in the cerebral cortex, striatum, and hippocampus, localizing to neuronal perikarya.
Conclusions:
- The novel adenylyl cyclase represents a potential physiological target mimicked by immunosuppressant-immunophilin complexes.
- Its enrichment in specific brain regions suggests a significant role in neuronal function and regulation.