Regulators of NFAT
Disclosed are methods of identifying an agent that modulates an NFAT regulator protein. One such method comprises contacting at least one test agent with a recombinant cell comprising at least one NFAT regulator protein or fragment or derivative thereof, assessing the effect of the test agent on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, and identifying the test agent that has an effect on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, whereby the identified test agent is characterized as an agent that modulates an NFAT regulator protein. Methods of identifying an agent that modulates intracellular calcium, methods to screen for an agent that modulates NFAT regulator function, methods to diagnose unexplained immunodeficiency in a subject, and methods for identifying an agent for treating or preventing a disease or disorder associated with a NFAT regulator protein or calcium signaling are also disclosed.
1. A recombinant cell comprising a heterologous nucleic acid encoding at least one mammalian Nuclear Factor of Activated T cells (NFAT) regulator protein that is an orai polypeptide, wherein the heterologous nucleic acid is a mammalian NFAT regulator gene, wherein the NFAT regulator gene is ORAI1; and the recombinant cell is an isolated cell.
2. An isolated recombinant cell comprising a heterologous mammalian ORAI1 gene and a heterologous mammalian stromal interaction molecule (STIM) gene.
3. The recombinant cell of claim 2 , wherein the cell is an isolated, mammalian, human, rodent, insect, or Xenopus cell.
4. The recombinant cell of claim 3 , wherein the ORAI1 gene and the STIM gene are human nucleic acid sequences.
5. The recombinant cell of claim 3 , wherein the ORAI1 gene and the STIM gene are expressed in the cell to produce heterologous ORAI1 and heterologous stromal interaction molecule (STIM) polypeptides.