Protein that makes memories last identified

Researchers have identified certain prion-like proteins that are essential for creating and maintaining long-term memories.

To ensure that long-lasting memories are created only in the appropriate neural circuits, Stowers researcher Kausik Si, who led the study, explains, the protein must be tightly regulated so that it adopts its prion-like form only in response to specific stimuli.

Si and his colleagues knew that Orb2 existed in two forms-Orb2A and Orb2B. Orb2B is widespread throughout the fruit fly's nervous system, but Orb2A appears only in a few neurons, at extremely low concentrations. What's more, once it is produced, Orb2A quickly falls apart; the protein has a half-life of only about an hour.

To look for leads, the scientists searched for proteins that physically interact with Orb2A. Because Orb2A is so scarce, finding it and identifying its molecular accomplices took perseverance and refinement of the standard protein-cataloging techniques. Post-doctoral researcher Erica White-Grindley led that effort, and after several years, turned up more than 60 suspected partners for Orb2A.

One of these proteins, TOB, doubled the half-life of Orb2A, thereby temporarily increasing its abundance. The scientists were skeptical that this boost in stability would be enough to reliably stabilize long-term memories, but further biochemical analyses led them to a more satisfying explanation.

Their experiments revealed that when TOB associates with Orb2A - which is known to occur in response to an incoming nerve signal-this triggers the addition of chemical tags known as phosphates to both of the proteins, altering both proteins' stability. Once phosphorylated, the TOB-Orb2A complex falls apart and Orb2A becomes much more stable, with a new half-life of 24 hours. This increases the prevalence of the prion-like state.

The new research has been published in the open access journal PLOS Biology.