Rapid macropinocytic transfer of α-synuclein to lysosomes.

Endosomes / metabolism Humans Lysosomes / metabolism Parkinson Disease / metabolism Synucleinopathies alpha-Synuclein / metabolism
CP: Neuroscience CP: cell biology MVB PFF Parkinson’s disease clathrin independent dopaminergic neurons endocytosis iPSC lysosomes macropinocytosis α-synuclein

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
19 07 2022
Historique:
received: 29 12 2021
revised: 10 05 2022
accepted: 22 06 2022
entrez: 20 7 2022
pubmed: 21 7 2022
medline: 23 7 2022
Statut: ppublish

Résumé

The nervous system spread of alpha-synuclein fibrils is thought to cause Parkinson's disease (PD) and other synucleinopathies; however, the mechanisms underlying internalization and cellular spread are enigmatic. Here, we use confocal and superresolution microscopy, subcellular fractionation, and electron microscopy (EM) of immunogold-labeled α-synuclein preformed fibrils (PFFs) to demonstrate that this form of the protein undergoes rapid internalization and is targeted directly to lysosomes in as little as 2 min. Uptake of PFFs is disrupted by macropinocytic inhibitors and circumvents classical endosomal pathways. Immunogold-labeled PFFs are seen at the highly curved inward edge of membrane ruffles, in newly formed macropinosomes, in multivesicular bodies and in lysosomes. While most fibrils remain in lysosomes, a portion is transferred to neighboring naive cells along with markers of exosomes. These data indicate that PFFs use a unique internalization mechanism as a component of cell-to-cell propagation.

Identifiants

DOI: 10.1016/j.celrep.2022.111102 PMID: 35858558
pubmed: 35858558
pii: S2211-1247(22)00904-4
doi: 10.1016/j.celrep.2022.111102
pii:
doi:

Substances chimiques

alpha-Synuclein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

111102

Informations de copyright

Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Armin Bayati (A)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Emily Banks (E)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Chanshuai Han (C)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Wen Luo (W)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Wolfgang E Reintsch (WE)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Cornelia E Zorca (CE)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Irina Shlaifer (I)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Esther Del Cid Pellitero (E)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Benoit Vanderperre (B)

Department of Biological Sciences, Université du Québec à Montréal, Montreal, QC, Canada.

Heidi M McBride (HM)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Edward A Fon (EA)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Thomas M Durcan (TM)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.

Peter S McPherson (PS)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada. Electronic address: peter.mcpherson@mcgill.ca.

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Classifications MeSH

questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Vésicules cytoplasmiques › Vésicules de transport › Endosomes › Rapid macropinocytic transfer of α-synuclein...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Rapid macropinocytic transfer of α-synuclein...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Vésicules cytoplasmiques › Lysosomes › Rapid macropinocytic transfer of α-synuclein...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Maladie de Parkinson › Rapid macropinocytic transfer of α-synuclein...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles de l'homéostasie des protéines › Synucléinopathies › Rapid macropinocytic transfer of α-synuclein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à la maladie de Parkinson › alpha-Synucléine › Rapid macropinocytic transfer of α-synuclein...