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Researchers used proximity proteomics to identify proteins present at synapses during active learning in C. elegans worms, rather than just examining snapshots after training was complete. They discovered that the enzyme cathepsin B (CPR-4 in worms) accumulates at synapses specifically during learning and is essential for memory formation. When CPR-4 was absent, worms could not learn effectively, and their synaptic protein profiles resembled those of untrained animals, suggesting the enzyme promotes learning by selectively clearing proteins to enable synaptic remodeling.
Why it matters
This work identifies a previously unknown mechanism by which the brain physically reorganizes neural connections during learning through targeted protein removal. Understanding how cathepsin B contributes to learning could eventually inform approaches to enhance memory formation or address learning deficits in neurological conditions.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Learning requires dynamic changes in synaptic protein composition. Most synaptic proteomic studies capture endpoint snapshots following training, overlooking molecular changes occurring during learning itself. We previously established TurboID proximity proteomics as an approach to capture protein-level changes during learning in the nervous system of Caenorhabditis elegans. Here, we apply this strategy to synapses. Trained synapses exhibited a distinct proteome compared with mock-trained controls, with pathways enriched for neurotransmission, synaptic reorganisation, protein trafficking, and autophagy. Enrichment of autophagy proteins led us to investigate the cathepsin B orthologue CPR-4, a previously uncharacterised candidate for learning identified exclusively in trained synapses. Functional validation identified CPR-4 as a novel regulator of memory: CPR-4 is required for learning, and the absence of CPR-4 results in trained synaptic proteomes that are more like those of mock-trained synapses. Our findings support a model through which CPR-4 promotes synaptic remodelling required for learning through targeted protein clearance.
Source: Synaptic proteomics identifies cathepsin B as a regulator of synapse remodelling during learning