Identification of Long Lived Synaptic Proteins by Comprehensive Proteomic Analysis of Synaptosome Protein Turnover

ABSTRACT: Memory formation is believed result from changes in synapse strength and structure. While memories may persist for the lifetime of an organism, the proteins and lipids that make up synapses undergo constant turnover with lifetimes from minutes to days. The molecular basis for memory maintenance may rely on a subset of long-lived proteins (LLPs). While it is known that LLPs exist, whether such proteins are present at synapses is unknown. We performed an unbiased screen using metabolic pulse-chase labeling in mice and cultured neurons combined with quantitative proteomics and identified synaptic LLPs with half-lives of several weeks or longer. Synaptic proteins generally exhibited longer lifetimes than cytosolic proteins. Protein turnover was sensitive to pharmacological manipulations of activity in neuronal cultures or in mice exposed to an enriched environment. We show that synapses contain LLPs and that global synapse protein turnover is modulated by neuronal activity and behavioral experience.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat) Mus Musculus (mouse)

TISSUE(S): Brain, Primary Neuron, Cell Culture, Kidney

SUBMITTER: chanhyun na  

LAB HEAD: Richard L. Huganir

PROVIDER: PXD007156 | Pride | 2018-03-19

REPOSITORIES: Pride