Calcineurin: Difference between revisions

Latest revision as of 11:51, 15 February 2025

Calcineurin[edit]

Calcineurin is a calcium and calmodulin-dependent serine/threonine protein phosphatase involved in a variety of cellular processes. It is a key player in the immune system, particularly in the activation of T-cells. Calcineurin is also important in the nervous system, where it regulates neuronal activity and synaptic plasticity.

Structure[edit]

Calcineurin is a heterodimeric protein composed of two subunits: the catalytic subunit A (PPP3CA) and the regulatory subunit B. The catalytic subunit contains the active site and is responsible for the phosphatase activity, while the regulatory subunit binds calcium ions and calmodulin, which are essential for the activation of calcineurin.

Function[edit]

Calcineurin plays a crucial role in the signal transduction pathways of T-cells. Upon activation by calcium and calmodulin, calcineurin dephosphorylates the nuclear factor of activated T-cells (NFAT), allowing it to translocate into the nucleus and activate the transcription of genes necessary for T-cell activation and proliferation.

In the nervous system, calcineurin is involved in the regulation of neurotransmitter release and long-term potentiation, which are critical for learning and memory.

Clinical Significance[edit]

Calcineurin inhibitors, such as cyclosporine and tacrolimus, are widely used as immunosuppressants in organ transplantation to prevent rejection. These drugs inhibit calcineurin activity, thereby suppressing T-cell activation and the immune response.

Related pages[edit]

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-'''Calcineurin''' (CN), also known as '''PPP3CA''', is a [[calcium]] and [[calmodulin]] dependent [[serine]]/[[threonine]] [[phosphatase]]. It plays a crucial role in various cellular processes, including [[T-cell activation]], [[neuronal]] and [[muscle]] development, and the regulation of [[protein synthesis]] and [[gene expression]]. Calcineurin is a target of the immunosuppressive drugs [[cyclosporin]] and [[tacrolimus]], which are used to prevent [[organ transplant]] rejection.
+{{DISPLAYTITLE:Calcineurin}}
+==Calcineurin==
+[[File:Protein_PPP3CA_PDB_1aui.png|thumb|right|300px|Structure of Calcineurin (PPP3CA)]]
+Calcineurin is a [[calcium]] and [[calmodulin]]-dependent [[serine/threonine protein phosphatase]] involved in a variety of cellular processes. It is a key player in the [[immune system]], particularly in the activation of [[T-cells]]. Calcineurin is also important in the [[nervous system]], where it regulates [[neuronal]] activity and [[synaptic plasticity]].
 ==Structure==
-Calcineurin is a heterodimer composed of a catalytic A subunit (CnA) and a regulatory B subunit (CnB). The A subunit contains a [[serine]]/[[threonine]] phosphatase domain, a [[calmodulin]]-binding domain, and an autoinhibitory domain that overlaps with the calmodulin-binding domain. The B subunit binds calcium ions and is necessary for the activation of the phosphatase activity of the A subunit.
+Calcineurin is a heterodimeric protein composed of two subunits: the catalytic subunit A (PPP3CA) and the regulatory subunit B. The catalytic subunit contains the active site and is responsible for the phosphatase activity, while the regulatory subunit binds calcium ions and calmodulin, which are essential for the activation of calcineurin.
 ==Function==
-Calcineurin dephosphorylates various proteins, including members of the [[nuclear factor of activated T-cells (NFAT)]] family of transcription factors. Dephosphorylation of NFAT proteins by calcineurin promotes their translocation into the nucleus, where they participate in the transcription of genes involved in T-cell activation. Besides its role in the immune system, calcineurin is involved in the development and function of the nervous system and skeletal muscle, and it has been implicated in the pathophysiology of several neurological and psychiatric disorders, including [[Alzheimer's disease]], [[Parkinson's disease]], and [[schizophrenia]].
+Calcineurin plays a crucial role in the [[signal transduction]] pathways of [[T-cells]]. Upon activation by calcium and calmodulin, calcineurin dephosphorylates the [[nuclear factor of activated T-cells]] (NFAT), allowing it to translocate into the nucleus and activate the transcription of genes necessary for T-cell activation and proliferation.
-==Regulation==
+In the nervous system, calcineurin is involved in the regulation of [[neurotransmitter]] release and [[long-term potentiation]], which are critical for learning and memory.
-Calcineurin activity is regulated by calcium and calmodulin. Upon an increase in intracellular calcium levels, calmodulin undergoes a conformational change that allows it to bind to calcineurin and activate its phosphatase activity. The activity of calcineurin is also modulated by its endogenous inhibitors, such as [[cabin-1]], [[AKAP79]], and the [[RCAN]] family of proteins, which can bind to calcineurin and inhibit its activity.
 ==Clinical Significance==
-Due to its critical role in T-cell activation, calcineurin is a key target for immunosuppressive therapy in organ transplantation. Cyclosporin and tacrolimus bind to the immunophilins [[cyclophilin]] and [[FKBP12]], respectively, and the resulting complexes inhibit calcineurin, thereby suppressing the immune response and preventing organ rejection. However, the use of calcineurin inhibitors is associated with several side effects, including nephrotoxicity, hypertension, and increased risk of infections and cancer. Research into the development of more selective calcineurin inhibitors or modulators continues, with the aim of reducing these side effects.
+Calcineurin inhibitors, such as [[cyclosporine]] and [[tacrolimus]], are widely used as [[immunosuppressants]] in organ transplantation to prevent rejection. These drugs inhibit calcineurin activity, thereby suppressing T-cell activation and the immune response.
-==See Also==
+==Related pages==
-* [[Immunosuppression]]
+* [[Protein phosphatase]]
-* [[Phosphatase]]
+* [[Calmodulin]]
-* [[T-cell activation]]
+* [[T-cell receptor]]
-* [[Cyclosporin]]
+* [[Immunosuppressant]]
-* [[Tacrolimus]]
-[[Category:Enzymes]]
+[[Category:Proteins]]
-[[Category:Cell biology]]
+[[Category:Signal transduction]]
 [[Category:Immunology]]
-{{Medicine-stub}}