Prion-like protein may be involved in memory

Prion-like proteins may hold the key to understanding how the brain forms lasting memories, according to the Nobel prize-winning researcher from Columbia University Prof Eric Kandel, who is in Australia for the Australian Neuroscience Society conference in Melbourne this week.

Kandel, who presented the ANS Overseas Lecture yesterday, described recently published research that implicates a prion-like protein called CPEB as a crucial component of retaining long-term memories. The protein is thought to act as a kind of molecular switch that activates local protein synthesis in synapses recruited during the formation of long-term memories.

But in a first for prion proteins, the stable and self-perpetuating form of the CPEB protein is the biologically active form. Other known prions, such as the one that has been linked to mad cow disease, cause correctly folded active proteins of the same type to misfold, ceasing their normal function and damaging the cell.

The discovery was made by one of Kandel's postdocs, Kausik Si, who was looking at how synapse specificity is facilitated in the formation of long term memory using Kandel's long-time favourite model for investigating memory mechanisms, the sea slug Aplysia.

Si identified the Aplysia CPEB protein as having prion-like properties, and yeast models were used to show that the protein in its prion conformation formed aggregates that bound to mRNA and activated local protein synthesis associated with the formation of new synapses.

"It's the first time that a self-perpetuating form of a prion-like protein is the active form of the protein," Kandel said.

He is now looking at how the protein is switched over to its active prion form, and suspects that the neurotransmitter serotonin may play a role in the conversion process. Investigation into the role of CPEB in mammalian neurons is also underway.

The Australian Neuroscience Society conference is continuing. For more stories from the conference, read the February issue of Australian Life Scientist magazine.