PXD038287

PXD038287 is an original dataset announced via ProteomeXchange.

Title	Differential intracellular trafficking of exosomes in microglia and astrocytes
Description	Exosomes have emerged as key players in cell-to-cell communication in both physiological and pathological processes in the Central Nervous System. Thus far, the intracellular pathways involved in uptake and trafficking of exosomes within different cell types of the brain are poorly understood. In our study, the endocytic processes and subcellular sorting of exosomes were investigated in primary glial cells, particularly linked with the exosome- associated α-synuclein (α-syn) transmission. Mouse microglia and astrocytic primary cultures were incubated with DiI-stained mouse brain-derived exosomes. The internalization and trafficking pathways were analysed in cells treated with pharmacological reagents that block the major endocytic pathways. Brain-derived exosomes were internalized by both glial cell types; however, uptake was more efficient in microglia than in astrocytes. Colocalization of exosomes with early and late endocytic markers (Rab5, Lamp1) indicated that exosomes are sorted to endolysosomes for subsequent processing. Treatment with Cytochalasin D, that blocks actin-dependent phagocytosis and/or macropinocytosis, inhibited exosome entry into glial cells, whereas treatment with inhibitors that strip off cholesterol from the plasma membrane, induced uptake, however differentially altered endosomal sorting. Exosome-associated fibrillar α-Syn was efficiently internalized and detected in Rab5- and Lamp1- positive compartments within microglia. Our study strongly suggests that exosomes enter glial cells through an actin network-dependent endocytic pathway and are sorted to endolysosomes for subsequent processing. Further, brain-derived exosomes are capable of mediating cell-to-glia transmission of pathological α-Syn that is also targeted to the endosomal pathway, suggesting a possible beneficial role in microglia-mediated clearance of toxic protein aggregates, present in numerous neurodegenerative diseases.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:03:00.455.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Samiotaki
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-22 04:10:05	ID requested
1	2023-07-20 11:02:53	announced
⏵ 2	2023-11-14 09:03:08	announced	2023-11-14: Updated project metadata.

Pantazopoulou M, Lamprokostopoulou A, Karampela DS, Alexaki A, Delis A, Coens A, Samiotaki M, Kriebardis AG, Melki R, Pagakis SN, Stefanis L, Vekrellis K, Differential intracellular trafficking of extracellular vesicles in microglia and astrocytes. Cell Mol Life Sci, 80(7):193(2023) [pubmed]

submitter keyword: brain-derived exosomes

α-synuclein KO mouse brain hemispheres (CD57BL6)

Kostas Vekrellis
contact affiliation	Biomedical Research Foundation Academy of Athens- BRFAA, Centre of Basic Research, Athens, Greece
contact email	vekrellis@bioacademy.gr
lab head
Martina Samiotaki
contact affiliation	Protein Analysis Laboratory B.S.R.C. "Alexander Fleming", Alexander Fleming Street 34 16672, Vari, Greece
contact email	samiotaki@fleming.gr
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/2023/07/PXD038287

PRIDE project URI

• PRIDE
  1. PXD038287
     1. Label: PRIDE project
     2. Name: Differential intracellular trafficking of exosomes in microglia and astrocytes