Identification of long-lived synaptic proteins by proteomic analysis of synaptosome protein turnover

Seok Heo, Graham H. Diering, Chan Hyun Na, Raja Sekhar Nirujogi, Julia L. Bachman, Akhilesh Pandey, Richard L. Huganir

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Memory formation is believed to 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 vivo in mice and in vitro in cultured neurons combined with quantitative proteomics. We identified synaptic LLPs with half-lives of several months or longer. Proteins in synaptic fractions generally exhibited longer lifetimes than proteins in cytosolic fractions. 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 that may underlie stabile long-lasting changes in synaptic structure and function.

Original languageEnglish (US)
Pages (from-to)E3827-E3836
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - Apr 17 2018


  • Enriched environment
  • Long-lived proteins
  • Mass spectrometry
  • Neuronal activity
  • Protein turnover

ASJC Scopus subject areas

  • General


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