Suzana Ulian-Benitez (left), Simon Bishop (middle), Alicia Hidalgo (right) and team have recently reported a novel mechanism of structural synaptic plasticity. A long-standing paradox had been that although learning, memory and synaptic plasticity in humans are thought to depend on the kinase function of Trk receptors for neurotrophin ligands, the most abundant isoforms in the adult brain lack the kinase domain.
Importantly, problems with these isoforms underlie major mental health disorders, but how they function was not understood. The Hidalgo team solved this mystery using the fruit-fly, Drosophila. Fruit-flies possess non-canonical ‘kinase-less’ neurotrophin Trk receptors for neurotrophins. The team has demonstrated that one of these, Kek-6, signals without kinase activity, by regulating a key plasticity molecule. By revealing a novel mechanism of how synapses work, these findings will have major implications for understanding also the human brain in health and disease.
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