Research ArticleOsmotic Stress

Brx Mediates the Response of Lymphocytes to Osmotic Stress Through the Activation of NFAT5

Science Signaling  10 Feb 2009:
Vol. 2, Issue 57, pp. ra5
DOI: 10.1126/scisignal.2000081

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Brx to the Rescue

Extracellular hyperosmolarity, due to differences in the concentrations of salts and macromolecules between the inside of the cell and its external environment, would result in the loss of water from the cell were it not for the protective effect of the osmotic response. This involves the production of intracellular osmolytes, molecules such as sorbitol and taurine, that increase osmotic pressure inside the cell and balance tonicity between the inside of the cell and the outside. The transcription factor nuclear factor of activated T cells 5 (NFAT5), an atypical member of the NFAT family, is an important regulator of the osmotic response, and its abundance is increased in lymphocytes exposed to a hyperosmolar environment, such as occurs in the thymus and spleen. Osmosensing by cells involves members of the Rho family of guanosine triphosphatases and p38 mitogen-activated protein kinase (MAPK). Kino et al. have now found a role for the guanine nucleotide exchange factor Brx (also known as AKAP13) in mediating the induction of nfat5 expression in response to osmotic stress in lymphocytes. This involved a physical interaction between Brx and c-Jun N-terminal kinase (JNK)–interacting protein 4 (JIP4), a scaffold protein that specifically activates p38 MAPK. In addition to exhibiting a poor hyperosmolar response, brx+/− mice had defective humoral immunity. Together, these data suggest that Brx mediates osmotic stress–induced expression of nfat5 and plays a role in modulating the immune response.