Calcineurin

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Crystallographic structure of calcineurin heterodimer composed of the catalytic (PPP3CA) and regulatory (PPP3R1) subunits.[1]

Calcineurin (CaN) is a

T cell response. Calcineurin is the target of a class of drugs called calcineurin inhibitors, which include ciclosporin, voclosporin, pimecrolimus and tacrolimus
.

Structure

Calcineurin is a heterodimer of a 61-kD calmodulin-binding catalytic subunit, calcineurin A and a 19-kD Ca2+-binding regulatory subunit, calcineurin B. There are three isozymes of the catalytic subunit, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two isoforms of the regulatory, also encoded by separate genes (PPP3R1, PPP3R2).

protein phosphatase 3, catalytic subunit, alpha isozyme
Identifiers
Symbol
Chr. 4 q24
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protein phosphatase 3, catalytic subunit, beta isozyme
Identifiers
Symbol
Chr. 10 q22.2
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protein phosphatase 3, catalytic subunit, gamma isozyme
Identifiers
Symbol
Chr. 8 p21.3
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protein phosphatase 3, regulatory subunit B, alpha
Identifiers
Symbol
Chr. 2 p14
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protein phosphatase 3, regulatory subunit B, beta
Identifiers
Symbol
Chr. 9 q31
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Mechanism of action

When an

T cell receptor on T cells, there is an increase in the cytoplasmic level of calcium, which activates calcineurin by binding a regulatory subunit and activating calmodulin binding.[3] Calcineurin induces transcription factors (NFATs) that are important in the transcription of IL-2 genes. IL-2 activates T-helper lymphocytes and induces the production of other cytokines. In this way, it governs the action of cytotoxic lymphocytes
. The amount of IL-2 being produced by the T-helper cells is believed to influence the extent of the immune response significantly.

Clinical relevance

Rheumatic diseases

Calcineurin inhibitors are prescribed for adult

Sjögren's syndrome (administered as ophthalmic emulsion).[4]

Schizophrenia

Calcineurin is linked to receptors for several brain chemicals including

GABA.[5] An experiment with genetically-altered mice that could not produce calcineurin showed similar symptoms as in humans with schizophrenia: impairment in working memory, attention deficits, aberrant social behavior, and several other abnormalities characteristic of schizophrenia.[6]

Diabetes

Calcineurin along with NFAT, may improve the function of diabetics'

beta cells.[7][8] Thus tacrolimus contributes to the frequent development of new diabetes following renal transplantation.[9]

Calcineurin/NFAT signaling is required for perinatal lung maturation and function.[10]

Organ transplantation

Calcineurin inhibitors such as tacrolimus are used to suppress the immune system in organ allotransplant recipients to prevent rejection of the transplanted tissue.[11]

Interactions

Calcineurin has been shown to

interact with RCAN1[12] and AKAP5.[13]

References

Further reading

External links