A WiNTers tale

The secreted WNT proteins activate two distinct signaling pathways: the canonical WNT/β-catenin pathway and a WNT/Ca²⁺ pathway that interferes with the canonical pathway. In the May 16 Nature, Saneyoshi etal. define NF-AT as a downstream target of the WNT/Ca²⁺ pathway (Nature 2002, 417:295-299).

Members of the NF-AT (nuclear factor of activated T cells) family play a pivotal role in the regulation of gene expression in T lymphocytes. NF-AT is translocated to the nucleus following activation by calcineurin in response to Ca²⁺ signaling. Saneyoshi etal. reasoned that NF-AT might play a role in ventral cell signaling in the WNT/Ca²⁺ pathway. To demonstrate this they cloned the Xenopus homologue of NF-AT (XNF-AT).

They found that XNF-AT showed Ca-dependent dephosphorylation during development, and that dephosphorylation lead to nuclear localization and transcriptional activation. Injection of an activated XNF-AT mutant lead to 'ventralized' Xenopus embryos, whereas a dominant-negative isoform induced a complete secondary dorsal axis. ...