PKMζ, but not PKCλ, is rapidly synthesized and degraded at the neuronal synapse

SF Palida, MT Butko, JT Ngo, MR Mackey… - Journal of …, 2015 - Soc Neuroscience
SF Palida, MT Butko, JT Ngo, MR Mackey, LA Gross, MH Ellisman, RY Tsien
Journal of Neuroscience, 2015Soc Neuroscience
Synthesizing, localizing, and stabilizing new protein copies at synapses are crucial factors in
maintaining the synaptic changes required for storing long-term memories. PKMζ 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 PKMζ stability in rat neurons to
better understand its role during information encoding and storage. We used TimeSTAMP …
Synthesizing, localizing, and stabilizing new protein copies at synapses are crucial factors in maintaining the synaptic changes required for storing long-term memories. PKMζ 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 PKMζ 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 PKMζ as well as a related atypical PKC, PKCλ. These reporters revealed that both PKMζ and PKCλ were upregulated after chemical LTP induction; however, these new PKMζ copies exhibited more rapid turnover than basally produced PKMζ, particularly in dendritic spines. In contrast to PKMζ, new PKCλ copies exhibited elevated stability. Stable information storage over long periods of time is more challenging the shorter the metabolic lifetime of the candidate molecules.
Soc Neuroscience