PXD060477-1

PXD060477 is an original dataset announced via ProteomeXchange.

Title	Extracellular matrix proteolysis maintains synaptic plasticity during brain development
Description	Synapses are highly dynamic during early brain development, enabling the rapid adaptations that occur as neural circuits remodel in response to experience. The extracellular matrix (ECM) has been proposed as a critical regulator of synaptic plasticity in the brain. However, the molecular mechanisms that regulate the ECM and their impact on structural plasticity of synapses during brain development are unknown. Here, using time lapse imaging of excitatory synapses in zebrafish hindbrain motor neurons during development we observed synapses that were both short lived (<6 hours), and longer lived (>24 hours). Loss of ECM via hyaluronidase digestion or genetic deletion of brevican preferentially destabilized short-lived synapses relative to stable synapses, leading to increased synapse density. Conversely, genetic loss of matrix metalloprotease 14 (MMP14) led to accumulation of brevican and stabilized short-lived synapses, resulting in increased synapse density. Zebrafish microglial processes contacted synapses and expressed cell surface MMP14. Microglial MMP14 was required for its effects on synapse numbers and brevican digestion both in zebrafish as well as in triculture from human induced pluripotent stem cells. These pathways also impacted motor habituation in freely swimming fish and were required for stress-induced synapse plasticity. Based on these findings, we propose a model whereby ECM accumulation during development increases the probability that a synapse will convert from dynamic to stable. These studies define a molecular mechanism whereby ECM remodeling by microglia promote synapse plasticity in the developing brain.
HostingRepository	PRIDE
AnnounceDate	2026-03-16
AnnouncementXML	Submission_2026-03-16_04:25:47.906.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Justin McKetney
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-04 13:04:31	ID requested
⏵ 1	2026-03-16 04:25:49	announced

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;

submitter keyword: synaptic plasticity, synapse,extracellular matrix, brain development

Danielle Swaney
contact affiliation	Quantitative Biosciences Institute (QBI), San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA;Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, USA
contact email	Swaney.Danielle@ucsf.edu
lab head
Justin McKetney
contact affiliation	University of California, San Francisco
contact email	justinmcketney@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/03/PXD060477

PRIDE project URI

• PRIDE
  1. PXD060477
     1. Label: PRIDE project
     2. Name: Extracellular matrix proteolysis maintains synaptic plasticity during brain development