PXD041125

PXD041125 is an original dataset announced via ProteomeXchange.

Title	Pathological deficit of Cystatin B impairs synaptic plasticity in EPM1 human cerebral organoids
Description	Cystatin B (CSTB) is a small protease inhibitor involved in cell proliferation and migration, and composition of extracellular matrix during brain development. Loss-of-function mutations in the gene encoding CSTB cause progressive myoclonic epilepsy 1 (EPM1). We previously demonstrated that CSTB is locally synthesized in the synaptosomes from rat brain and secreted into the media, indicating its role in synaptic plasticity. In this work, we further investigate the involvement of CSTB in synaptic plasticity, using synaptosomes from rodents’ brain, as well as from human Cerebral Organoids (hCOs). Our data demonstrated that CSTB is released by synaptosomes in two ways: as a soluble protein, and in extracellular vesicles-mediated manner. Synaptosomes isolated from hCOs are enriched in pre-synaptic proteins, as expected for an in vitro model of human synapses, and contain CSTB at all developmental stages analysed. However, only at late maturation stages synapse becomes physiologically active, i.e. particularly enriched with exocytosis-associated proteins. CSTB presence in the synaptic territories was confirmed also by immunostaining on human neurons in vitro. To investigate if the depletion of CSTB in EPM1 is affecting synaptic plasticity, we used synaptosomes from EPM1 hCOs. The synaptosomal levels of presynaptic proteins and of an initiation factor linked to local protein synthesis, were reduced in EPM1 hCOs compared to controls, and the extracellular vesicles trafficking was impaired. Moreover, morphological alteration was detected in neurons from EPM1 patients, indicating a connectivity deficit. In conclusion, our data indicate a significant role of synaptic CSTB in cell-to-cell communication in physiological and pathological conditions, and demonstrated that CSTB-dependent altered synaptic plasticity is one of the mechanisms underlying EPM1.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:54:12.759.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Angela Chambery
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-27 03:48:37	ID requested
1	2024-08-10 12:07:17	announced
⏵ 2	2024-10-22 06:54:13	announced	2024-10-22: Updated project metadata.

10.1007/s12035-023-03812-y;

Pizzella A, Penna E, Abate N, Frenna E, Canafoglia L, Ragona F, Russo R, Chambery A, Perrone-Capano C, Cappello S, Crispino M, Di Giaimo R, Pathological Deficit of Cystatin B Impairs Synaptic Plasticity in EPM1 Human Cerebral Organoids. Mol Neurobiol, 61(7):4318-4334(2024) [pubmed]

submitter keyword: EPM1

cystatin B

synaptic plasticity

Angela Chambery
contact affiliation	Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Caserta, Italy
contact email	angela.chambery@unicampania.it
lab head
Angela Chambery
contact affiliation	University of Campania "Luigi Vanvitelly"
contact email	angela.chambery@unicampania.it
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/2024/08/PXD041125

PRIDE project URI

• PRIDE
  1. PXD041125
     1. Label: PRIDE project
     2. Name: Pathological deficit of Cystatin B impairs synaptic plasticity in EPM1 human cerebral organoids