Regulation of exocytosis and mitochondrial relocalization by Alpha-synuclein in a mammalian cell model.
Cell biology
Cellular neuroscience
Microscopy
Parkinson's disease
Journal
NPJ Parkinson's disease
ISSN: 2373-8057
Titre abrégé: NPJ Parkinsons Dis
Pays: United States
ID NLM: 101675390
Informations de publication
Date de publication:
2019
2019
Historique:
received:
19
11
2018
accepted:
23
05
2019
entrez:
3
7
2019
pubmed:
3
7
2019
medline:
3
7
2019
Statut:
epublish
Résumé
We characterized phenotypes in RBL-2H3 mast cells transfected with human alpha synuclein (a-syn) using stimulated exocytosis of recycling endosomes as a proxy for similar activities of synaptic vesicles in neurons. We found that low expression of a-syn inhibits stimulated exocytosis and that higher expression causes slight enhancement. NMR measurements of membrane interactions correlate with these functional effects: they are eliminated differentially by mutants that perturb helical structure in the helix 1 (A30P) or NAC/helix-2 (V70P) regions of membrane-bound a-syn, but not by other PD-associated mutants or C-terminal truncation. We further found that a-syn (but not A30P or V70P mutants) associates weakly with mitochondria, but this association increases markedly under conditions of cellular stress. These results highlight the importance of specific structural features of a-syn in regulating vesicle release, and point to a potential role for a-syn in perturbing mitochondrial function under pathological conditions.
Identifiants
pubmed: 31263746
doi: 10.1038/s41531-019-0084-6
pii: 84
pmc: PMC6597712
doi:
Types de publication
Journal Article
Langues
eng
Pagination
12Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM117552
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG019391
Pays : United States
Organisme : NCRR NIH HHS
ID : C06 RR015495
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025502
Pays : United States
Organisme : NIH HHS
ID : S10 OD016320
Pays : United States
Organisme : NIH HHS
ID : S10 OD018509
Pays : United States
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing interests.
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