サブ細胞内でのインポルチンβ1の枯渇は、シナプス前局所翻訳と空間記憶を損なう

Axonal localization and local translation of mRNA encoding importin β1 are important for retrograde injury signaling and axonal growth. Here, we found that loss of importin β1 in axons through deletion of the mRNA's 3' untranslated region (3'UTR) caused a specific spatial memory deficit in mice. Electrophysiological analyses of hippocampal circuits revealed that mice expressing importin β1 transcripts lacking the 3'UTR (∆3'UTR) had impaired long-term potentiation (LTP) in presynaptic mossy fibers. Furthermore, mass spectrometry revealed an altered synaptic proteome and phosphoproteome, and sequencing of ribosome-associated RNAs showed suppression of locally translated presynaptic mRNAs in dentate gyrus neurons from mice expressing ∆3'UTR importin β1. This dysregulation was reflected in a reduction in the readily releasable pool of synaptic vesicles in mossy fiber synapses. Thus, axonal localization of importin β1-encoding mRNA is required to shape the presynapse, and disruption of this mechanism causes memory deficits.