The nuclear import of Frizzled2-C by Importins-β11 and α2 promotes postsynaptic development

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Abstract
In Drosophila, activation by Wingless results in cleavage of its Frizzled2 receptor and translocation of the C terminus (Fz2-C) from the postsynaptic density to the nuclei. Mosca and Schwarz find that nuclear Fz2-C entry requires the nuclear import factors Importin-β11 and Importin-α2. This pathway promotes postsynaptic development of the subsynaptic reticulum. Synapse-to-nucleus signaling is critical for synaptic development and plasticity. In Drosophila, the ligand Wingless causes the C terminus of its Frizzled2 receptor (Fz2-C) to be cleaved and translocated from the postsynaptic density to nuclei. The mechanism of nuclear import is unknown and the developmental consequences of this translocation are uncertain. We found that Fz2-C localization to muscle nuclei required the nuclear import factors Importin-β11 and Importin-α2 and that this pathway promoted the postsynaptic development of the subsynaptic reticulum (SSR), an elaboration of the postsynaptic plasma membrane. importin-β11 (imp-β11) and dfz2 mutants had less SSR, and some boutons lacked the postsynaptic marker Discs Large. These developmental defects in imp-β11 mutants could be overcome by expression of Fz2-C fused to a nuclear localization sequence that can bypass Importin-β11. Thus, Wnt-activated growth of the postsynaptic membrane is mediated by the synapse-to-nucleus translocation and active nuclear import of Fz2-C via a selective Importin-β11/α2 pathway.