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Nat Neurosci. 2010 Aug;13(8):935-43. doi: 10.1038/nn.2593. Epub 2010 Jul 4.

The nuclear import of Frizzled2-C by Importins-beta11 and alpha2 promotes postsynaptic development.

Author information

1
The F.M. Kirby Neurobiology Center, Children's Hospital Boston, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

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-beta11 and Importin-alpha2 and that this pathway promoted the postsynaptic development of the subsynaptic reticulum (SSR), an elaboration of the postsynaptic plasma membrane. importin-beta11 (imp-beta11) and dfz2 mutants had less SSR, and some boutons lacked the postsynaptic marker Discs Large. These developmental defects in imp-beta11 mutants could be overcome by expression of Fz2-C fused to a nuclear localization sequence that can bypass Importin-beta11. 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-beta11/alpha2 pathway.

PMID:
20601947
PMCID:
PMC2913881
DOI:
10.1038/nn.2593
[Indexed for MEDLINE]
Free PMC Article

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