A brain atlas of synapse protein lifetime across the mouse lifespan

Autor: Edita Bulovaite, Zhen Qiu, Maximilian Kratschke, Adrianna Zgraj, David G. Fricker, Eleanor J. Tuck, Ragini Gokhale, Babis Koniaris, 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
Přispěvatelé: European Research Council, European Commission, Autism Research Foundation, Wellcome Trust, Cajal Blue Brain, Ministerio de Ciencia e Innovación (España), National Institute of Mental Health (Czech Republic), Swiss National Science Foundation, National Centres of Competence in Research (Switzerland), Spastic Paraplegia Foundation
Rok vydání: 2022
Předmět:
Zdroj: Neuron
Bulovaite, E, Qiu, Z, Kratschke, M, Zgraj, A, Fricker, D G, Tuck, E J, Gokhale, R, Koniaris, B, Jami, S A, Merino-Serrais, P, Husi, E, Mendive-Tapia, L, Vendrell, M, O'Dell, T J, DeFelipe, J, Komiyama, N H, Holtmaat, A, Fransén, E & Grant, S G N 2022, ' A brain atlas of synapse protein lifetime across the mouse lifespan ', Neuron . https://doi.org/10.1016/j.neuron.2022.09.009
DOI: 10.1016/j.neuron.2022.09.009
Popis: 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.
Sarah Lempriere, Cathy McLaughlin, Emma Sigfridsson, Rand Dahan, Gabor Varga, Emily Robson, Theresa Wong, Bev Notman, Ian Hawes, Dimitra Koukaroudi, William Mungall, and Fabio De Moliner for technical assistance. Colin Davey for editing. Debbie Maizels for artwork. Trevor Robbins, Szu-Han Wang, Tim Bussey for comments on the manuscript. Funding: S.G.N.G.: The European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (695568 SYNNOVATE), Simons Foundation Autism Research Initiative (529085), and the Wellcome Trust (Technology Development Grant 202932). J.D.: Interdisciplinary Platform Cajal Blue Brain (CSIC, Spain). P.M.-S.: Spanish Ministerio de Ciencia e Innovación (IJCI-2016-27658). T.J.O.: National Institute of Mental Health Grant (R01MH060919-15). A.H.: Swiss National Science Foundation (grant 31003A_173125), the Swiss National Centre Competence in Research (NCCR) Synapsy (grant 51NF40-185897), and a gift from a private foundation with public interest through the International Foundation for Research in Paraplegia (chair Alain Rossier). For the purpose of open access, the author has applied a CC-BY public copyright license to any author accepted manuscript version arising from this submission.
Databáze: OpenAIRE