PKM{zeta}, But Not PKC{lambda}, Is Rapidly Synthesized and Degraded at the Neuronal Synapse

Synthesizing, localizing, and stabilizing new protein copies at synapses are crucial factors in maintaining the synaptic changes required for storing long-term memories. PKM recently emerged as a molecule putatively responsible for maintaining encoded memories over time because its presence correlates with late LTP and because its inhibition disrupts LTP in vitro and long-term memory storage in vivo. Here we investigated PKM stability in rat neurons to better understand its role during information encoding and storage. We used TimeSTAMP reporters to track the synthesis and degradation of PKM as well as a related atypical PKC, PKC. These reporters revealed that both PKM and PKC were upregulated after chemical LTP induction; however, these new PKM copies exhibited more rapid turnover than basally produced PKM, particularly in dendritic spines. In contrast to PKM, new PKC copies exhibited elevated stability. Stable information storage over long periods of time is more challenging the shorter the metabolic lifetime of the candidate molecules.