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A brain atlas of synapse protein lifetime across the mouse lifespan

Bulovaite, Edita; Qiu, Zhen; Kratschke, Maximilian; Zgraj, Adrianna; Fricker, David G.; Tuck, Eleanor J.; Gokhale, Ragini; Koniaris, Babis; Jami, Shekib A.; Merino-Serrais, Paula; Husi, Elodie; Mendive-Tapia, Lorena; Vendrell, Marc; O’Dell, Thomas J.; DeFelipe, Javier; Komiyama, Noboru H.; Holtmaat, Anthony; Fransén, Erik; Grant, Seth G.N.


Edita Bulovaite

Zhen Qiu

Maximilian Kratschke

Adrianna Zgraj

David G. Fricker

Eleanor J. Tuck

Ragini Gokhale

Shekib A. Jami

Paula Merino-Serrais

Elodie Husi

Lorena Mendive-Tapia

Marc Vendrell

Thomas J. O’Dell

Javier DeFelipe

Noboru H. Komiyama

Anthony Holtmaat

Erik Fransén

Seth G.N. Grant


The lifetime of proteins in synapses is important for their signaling, maintenance, and remodeling, and for memory duration. We quantified the lifetime of endogenous PSD95, an abundant postsynaptic protein in excitatory synapses, at single-synapse resolution across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of PSD95 lifetimes extending from hours to several months, with distinct spatial distributions in dendrites, neurons, and brain regions. Synapses with short protein lifetimes are enriched in young animals and in brain regions controlling innate behaviors, whereas synapses with long protein lifetimes accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. Synapse protein lifetime increases throughout the brain in a mouse model of autism and schizophrenia. Protein lifetime adds a further layer to synapse diversity and enriches prevailing concepts in brain development, aging, and disease.

Journal Article Type Article
Acceptance Date Sep 7, 2022
Online Publication Date Oct 5, 2022
Publication Date 2022-12
Deposit Date Nov 21, 2022
Publicly Available Date Nov 22, 2022
Journal Neuron
Print ISSN 0896-6273
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 110
Issue 24
Pages 4057-4073
Keywords synapse proteome, postsynaptic density, proteostasis, synaptome, protein turnover, aging, brain development, autism, dendritic spine, pyramidal neuron, HaloTag
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