DJ-1 deficiency impairs synaptic vesicle endocytosis and reavailability at nerve terminals.
Proc Natl Acad Sci U S A
; 115(7): 1629-1634, 2018 02 13.
Article
en En
| MEDLINE
| ID: mdl-29386384
ABSTRACT
Mutations in DJ-1 (PARK7) are a known cause of early-onset autosomal recessive Parkinson's disease (PD). Accumulating evidence indicates that abnormalities of synaptic vesicle trafficking underlie the pathophysiological mechanism of PD. In the present study, we explored whether DJ-1 is involved in CNS synaptic function. DJ-1 deficiency impaired synaptic vesicle endocytosis and reavailability without inducing structural alterations in synapses. Familial mutants of DJ-1 (M26I, E64D, and L166P) were unable to rescue defective endocytosis of synaptic vesicles, whereas WT DJ-1 expression completely restored endocytic function in DJ-1 KO neurons. The defective synaptic endocytosis shown in DJ-1 KO neurons may be attributable to alterations in membrane cholesterol level. Thus, DJ-1 appears essential for synaptic vesicle endocytosis and reavailability, and impairment of this function by familial mutants of DJ-1 may be related to the pathogenesis of PD.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Sinapsis
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Vesículas Sinápticas
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Endocitosis
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Proteína Desglicasa DJ-1
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Terminaciones Nerviosas
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article