@article{89258cc68f73440fa54180524de5d4df,
title = "Identification of long-lived synaptic proteins by proteomic analysis of synaptosome protein turnover",
abstract = "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.",
keywords = "Enriched environment, Long-lived proteins, Mass spectrometry, Neuronal activity, Protein turnover",
author = "Seok Heo and Diering, {Graham H.} and Na, {Chan Hyun} and Nirujogi, {Raja Sekhar} and Bachman, {Julia L.} and Akhilesh Pandey and Huganir, {Richard L.}",
note = "Funding Information: We thank all members of the R.L.H. laboratory for helpful comments, discussion, and critical reading of the manuscript. We also thank Drs. Min-Sik Kim and Gajanan J. Sathe for helping design experimental approach and proteomic data acquisition. This work was supported by NIH Grants P50MH100024 and R01NS036715 (to R.L.H.) and P50NS038377 and R01CA184165 (to A.P.), NIH shared instrumentation Grant S10OD021844 (to A.P.), and the Center for Proteomics Discovery at Johns Hopkins University and the Canadian Institute for Health Research (G.H.D.). Funding Information: ACKNOWLEDGMENTS. We thank all members of the R.L.H. laboratory for helpful comments, discussion, and critical reading of the manuscript. We also thank Drs. Min-Sik Kim and Gajanan J. Sathe for helping design experimental approach and proteomic data acquisition. This work was supported by NIH Grants P50MH100024 and R01NS036715 (to R.L.H.) and P50NS038377 and R01CA184165 (to A.P.), NIH shared instrumentation Grant S10OD021844 (to A.P.), and the Center for Proteomics Discovery at Johns Hopkins University and the Canadian Institute for Health Research (G.H.D.). Publisher Copyright: {\textcopyright} 2018 National Academy of Sciences. All Rights Reserved.",
year = "2018",
month = apr,
day = "17",
doi = "10.1073/pnas.1720956115",
language = "English (US)",
volume = "115",
pages = "E3827--E3836",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "16",
}