Dataset Information

Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory

ABSTRACT: Experience-dependent learning depends on synaptic plasticity. Recent findings show that effective integration of novel salient information requires coordinated processes of homo- and hetero- synaptic plasticity onto neighboring dendritic branches. In this work, we hypothesized that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to this mechanism. We show that clusters of the peri-synaptic ECM proteoglycans, containing 6- and 2,6-sulfated chondroitin sulfates recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. CS56 co-immunoprecipitation of synaptosomal proteins identified several CS56-carrying/binding synaptic molecules that are implicated in Ca2+ signaling, vesicles cycling and AMPA-receptor exocytosis, thus suggesting their pivotal role in long-term potentiation (LTP). Finally, we demonstrated that the attenuation of CS56 glycoepitopes in the CA1 hippocampal region, through the depletion of versican as one of its main carriers, impairs LTP and object location memory in adult mice. These findings show that specific ECM glycans regulates the molecular mechanisms underlying induction and consolidation of synaptic plasticity, confirming that experience-dependent refinement of the brain ECM plays a critical role in learning and memory.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Manveen Sethi

LAB HEAD: Joseph Zaia

PROVIDER: PXD047129 | Pride | 2024-05-10

REPOSITORIES: Pride

ACCESS DATA

Publications

Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory in mice.

Chelini Gabriele G Mirzapourdelavar Hadi H Durning Peter P Baidoe-Ansah David D Sethi Manveen K MK O'Donovan Sinead M SM Klengel Torsten T Balasco Luigi L Berciu Cristina C Boyer-Boiteau Anne A McCullumsmith Robert R Ressler Kerry J KJ Zaia Joseph J Bozzi Yuri Y Dityatev Alexander A Berretta Sabina S

Cell reports 20240425 5

Recent findings show that effective integration of novel information in the brain requires coordinated processes of homo- and heterosynaptic plasticity. In this work, we hypothesize that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to these processes. We show that clusters of the peri-synaptic ECM, recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. Using CS56 co ...[more]

PMID: 38676925

Similar Datasets

Project description:Glioblastoma (GBM) is the most common and malignant primary brain tumor. The extracellular matrix (ECM), also known as the matrisome, helps determine glioma invasion, adhesion, and growth. Little attention, however, has been paid to glycosylation of the ECM components that constitute the majority of glycosylated protein mass and presumed biological properties. To acquire a comprehensive understanding of the biological functions of the matrisome and its components, including proteoglycans and glycosaminoglycans (GAGs), in GBM tumorigenesis, and to identify potential biomarker candidates, we studied the alterations of GAGs, including heparan sulfate (HS) and chondroitin sulfate (CS), the core proteins of proteoglycans, and other glycosylated matrisomal proteins in GBM subtypes vs. control human brain tissue samples. We scrutinized the proteomics data to acquire in-depth site-specific glycoproteomic profiles of the GBM subtypes that will assist in identifying specific glycosylation changes in GBM. We observed an increase in CS 6-O sulfation and a decrease in HS 6-O sulfation, accompanied by an increase in unsulfated CS and HS disaccharides in GBM vs. control samples. Several core matrisome proteins, including proteoglycans (decorin, biglycan, agrin, prolargin, glypican-1, CSPG4), tenascin, fibronectin, hyaluronan link protein 1 and 2, laminins, and collagens, were differentially regulated in GBM vs. controls. Interestingly, a higher degree of collagen hydroxyprolination was also observed for GBM vs. controls. Further, two proteoglycans, CSPG4 and agrin, were significantly lower, about 6–fold for IDH-mutant compared to the WT GBM samples. Differential regulation of O-glycopeptides for proteoglycans, including brevican, neurocan, and versican, was observed for GBM subtypes vs. controls. Moreover, an increase in levels of glycosyltransferase and glycosidase enzymes was observed for GBM when compared to control samples. We also report distinct protein, peptide, and glycopeptide features for GBM subtypes comparisons. Taken together, our study informs understanding of the alterations to key matrisomal molecules that occur during GBM development.

Dataset Information

Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory

Publications

Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure