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PXD069328

PXD069328 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleExtracellular matrix proteolysis maintains synapse plasticity during brain development
DescriptionMaintaining a dynamic neuronal synapse pool is critical to brain development. The extracellular matrix (ECM) regulates synaptic plasticity via mechanisms that are still being defined and are studied predominantly in adulthood. Using live imaging of excitatory synapses in zebrafish hindbrain we observed a bimodal distribution of short-lived (dynamic) and longer-lived (stable) synapses. Disruption of ECM via digestion or brevican deletion destabilized dynamic synapses and led to decreased synapse density. Conversely, loss of matrix metalloproteinase 14 (MMP14) led to accumulation of brevican and increased the lifetime of the dynamic synapse pool without affecting stable synapse pool, resulting in increased synapse density. Microglial MMP14 was essential to these effects in both fish and human iPSC-derived cultures. Both MMP14 and brevican were required for experience-dependent synapse plasticity in a motor learning assay. These data, complemented by mathematical modeling, define an essential role of ECM remodeling in maintaining a dynamic subset of synapses during brain development.
HostingRepositoryPRIDE
AnnounceDate2026-03-16
AnnouncementXMLSubmission_2026-03-16_03:59:55.030.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRobert Chalkley
SpeciesList scientific name: Danio rerio (Zebrafish) (Brachydanio rerio); NCBI TaxID: NEWT:7955;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-10-10 11:17:01ID requested
12026-03-16 03:59:56announced
Publication List
Nakajo H, Cao R, Mula SA, McKetney J, Silva NJ, Li KH, Chalkley RJ, Randolph LK, Shah M, Rose IVL, Kampmann M, Swaney DL, Kirst C, Molofsky AV, Extracellular matrix proteolysis maintains synapse plasticity during brain development. Nat Neurosci, 29(3):567-580(2026) [pubmed]
10.1038/s41593-025-02153-4;
Keyword List
submitter keyword: Zebra Fish
Brain
LC-MSMS
Extracellular
Biotinylation
Contact List
Robert Chalkley
contact affiliationUniversity of California San Francisco
contact emailrobert.chalkley@ucsf.edu
lab head
Robert Chalkley
contact affiliationUniversity of California San Francsico
contact emailrobert.chalkley@ucsf.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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