ArticleProceedings of the National Academy of Sciences of the United States of America2015
SPARC triggers a cell-autonomous program of synapse elimination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Modular Platform for Rapidly Investigating Long-Distance Propagation of Human Neural Network Activity.Advanced healthcare materials · 2026Article
- Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders.Current neuropharmacology · 2026Review
- Roles of Glia in Synapse Nano-organization.Advances in neurobiology · 2026Review
- The human neural cell atlas of Zika virus infection in developing brain tissue.Cell reports. Medicine · 2025Article
- Pathological PNPase variants with altered RNA binding and degradation activity affect the phenotype of bacterial and human cell models.NAR molecular medicine · 2025Article
- Astrocyte Regulation of Synapse Formation, Maturation, and Elimination.Cold Spring Harbor perspectives in biology · 2024Review
- Myokines: metabolic regulation in obesity and type 2 diabetes.Life metabolism · 2024Review
- GP60 and SPARC as albumin receptors: key targeted sites for the delivery of antitumor drugs.Frontiers in pharmacology · 2024Review
- Diosgenin restores memory function via SPARC-driven axonal growth from the hippocampus to the PFC in Alzheimer's disease model mice.Molecular psychiatry · 2023Article
- Extracellular matrix and synapse formation.Bioscience reports · 2023Article
- Changes in the Brain Extracellular Matrix Composition in schizophrenia: A Pathophysiological Dysregulation and a Potential Therapeutic Target.Cellular and molecular neurobiology · 2022Article
- Improved post-stroke spontaneous recovery by astrocytic extracellular vesicles.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points.Frontiers in molecular neuroscience · 2022Article
- Axon terminals control endolysosome diffusion to support synaptic remodelling.Life science alliance · 2021Article
- Interplay between hevin, SPARC, and MDGAs: Modulators of neurexin-neuroligin transsynaptic bridges.Structure (London, England : 1993) · 2021Article
- Roles of the synaptic molecules Hevin and SPARC in mouse neuromuscular junction development and repair.Neuroscience letters · 2021Article
- The role of astrocyte-mediated plasticity in neural circuit development and function.Neural development · 2021Review
- Astrocyte-Neuron Signaling in Synaptogenesis.Frontiers in cell and developmental biology · 2021Review
- Review
- Synapse elimination activates a coordinated homeostatic presynaptic response in an autaptic circuit.Communications biology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elimination of the excess synaptic contacts established in the early stages of neuronal development is required to refine the function of neuronal circuits. Here we investigate whether secreted protein acidic and rich in cysteine (SPARC), a molecule produced by glial cells, is involved in synapse removal. SPARC production peaks when innervation of the rat superior cervical ganglion and the tail of Xenopus tropicalis tadpoles are remodeled. The formation of new cholinergic synapses in autaptic single-cell microcultures is inhibited by SPARC. The effect resides in the C-terminal domain, which is also responsible for triggering a concentration- and time-dependent disassembly of stable cholinergic synapses. The loss of synaptic contacts is associated with the formation of retracted axon terminals containing multivesicular bodies and secondary lysosomes. The biological relevance of in vitro results was supported by injecting the tail of Xenopus tropicalis tadpoles with peptide 4.2, a 20-aa sequence derived from SPARC that mimics full-length protein effects. Swimming was severely impaired at ∼5 h after peptide application, caused by the massive elimination of neuromuscular junctions and pruning of axonal branches. Effects revert by 6 d after injection, as motor innervation reforms. In conclusion, SPARC triggers a cell-autonomous program of synapse elimination in cholinergic neurons that likely occurs when protein production peaks during normal development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.