NFAT works with neurotrophic signalling to regulate axon outgrowth in several neuronal populations. Additionally, NFAT transcription complexes integrate neuronal growth with guidance cues such as netrin to facilitate the formation of new synapses, helping to build neural circuits in the brain.

What does NFAT regulate?

Initially discovered in T cells, the NFAT gene family, consisting of five members, regulates immune system, inflammatory response, angiogenesis, cardiac valve formation, myocardial development, axonal guidance, skeletal muscle development, bone homeostasis, development and metastasis of cancer, and many other …

What activates NFAT?

Nuclear factor of activated T cells (NFAT) is a transcription factor regulated by calcium influx. When phosphorylated, it is confined to the cell cytoplasm where it is inactive. After T-cell activation, the ensuing calcium influx activates the phosphatase calcineurin that activates NFAT by dephosphorylating it.

What genes does NFAT regulate?

Facts

  • NFAT proteins regulate cell cycle-, apoptosis-, angiogenesis- and metastasis-related genes;
  • Although they bind to the same DNA sequence, different NFAT members and even isoforms have both redundant and opposite functions;

What is NFAT protein?

NFAT proteins are dephosphorylated by activated calcineurin, which leads to their nuclear translocation and the induction of NFAT-mediated gene transcription. During T-cell activation, it is the engagement of the T-cell receptor (TCR) that activates the calcium–calcineurin–NFAT pathway.

What is NFAT reporter?

The NFAT Reporter – Hek293 cell line contains a firefly luciferase gene under the control of NFAT response element stably integrated into Hek293 cells. This cell line is validated for the response to the stimulation of phorbol 12-myristate 13-acetate (PMA) with ionomycin.

How does calcineurin activate NFAT?

Once SLE T cells are activated through their TCR, Ca2+ influx increases, which induces calcineurin-mediated NFAT translocation to the nuclei, and then promotes transcriptional upregulation of CD40 ligand, a co-stimulatory molecule that induces antibody production and dendritic cell activation (99).

What is the Mef2 gene?

Mef2 is a critical regulator in heart development and cardiac gene expression. In vertebrates, there are four genes in the Mef2 transcription factor family: Mef2a, Mef2b, Mef2c, and Mef2d. Each is expressed at specific times during development.

What is NFAT in T cells?

It has also become clear that NFAT proteins have crucial roles in the development and function of the immune system. In T cells, NFAT proteins not only regulate activation but also are involved in the control of thymocyte development, T-cell differentiation and self-tolerance.

What is calcineurin phosphatase?

Calcineurin (also called protein phosphatase 2B) is a calcium/calmodulin-activated serine/threonine phosphatase that, once stimulated, de-phosphorylates and thereby activates the NFAT transcription factor.81. From: Cellular and Molecular Pathobiology of Cardiovascular Disease, 2014.

What is the role of NFAT in T cells?

T cells express three of the four calcium-regulated NFAT proteins: NFAT1, NFAT2 and NFAT4. These proteins are key regulators of T-cell activation, differentiation and development. In T cells, NFAT proteins are activated following T-cell receptor (TCR) ligation.

Why are NFAT proteins so versatile?

The functional versatility of NFAT proteins can be explained by their complex mechanism of regulation and their ability to integrate calcium signalling with other signalling pathways. This Review focuses on the recent advances in our understanding of the regulation, mechanism of action and functions of NFAT proteins in T cells.

What is the NFAT family of transcription factors?

Since the discovery of the first nuclear factor of activated T cells (NFAT) protein more than a decade ago, the NFAT family of transcription factors has grown to include five members. It has also become clear that NFAT proteins have crucial roles in the development and function of the immune system.

What triggers the activation of NFAT?

Figure 2: Regulation of NFAT activation. Ligation of the T-cell receptor (TCR) triggers the activation of receptor-associated tyrosine kinases that lead to the activation of phospholipase C-γ (PLC-γ). Activated PLC-γ causes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns (4,5)P 2 ), which generates inositol-1,4]