Despite the extensive study of the Wingless (Wg) or Wnt signaling pathway in regulating development and cancer, a previously unrecognized mechanism has been uncovered for Wg signaling at developing synapses in the Drosophila nervous system. Mathew et al. (see the Perspective by Arias) found that the Wg receptor DFrizzled2 can be cleaved and translocated from the plasma membrane to the area of the cell just outside the nucleus. In response to Wg signals, the C-terminal portion of the receptor then enters the nucleus, where it might act to regulate gene expression. Expression of an Fz2 mutant that could not be cleaved failed to rescue synapse formation in flies that expressed a mutant of Fz2 with defective signaling.
D. Mathew, B. Ataman, J. Chen, Y. Zhang, S. Cumberledge, V. Budnik, Wingless signaling at synapses is through cleavage and nuclear import of receptor DFrizzled2. Science 310, 1344-1347 (2005). [Abstract] [Full Text]