Evidence for a clathrin-independent endocytic pathway for APP internalization in the neuronal somatodendritic compartment.
Cell Rep
; 42(7): 112774, 2023 07 25.
Article
em En
| MEDLINE
| ID: mdl-37450368
ABSTRACT
Amyloid precursor protein (APP) internalization via clathrin-/dynamin-mediated endocytosis (CME) mediated by its YENPTY motif into endosomes containing ß-secretase is proposed to be critical for amyloid-beta (Aß) production. Here, we show that somatodendritic APP internalization in primary rodent neurons is not blocked by inhibiting dynamin or mutating the YENPTY motif, in contrast to non-neuronal cell lines. These phenomena, confirmed in induced human neurons under dynamin inhibition, occur during basal conditions and chemical long-term-depression stimulus, pointing to a clathrin-independent internalization pathway for somatodendritic APP. Mutating the YENPTY motif does not alter APP recycling, degradation, or endolysosomal colocalization. However, both dynamin inhibition and the YENPTY mutant significantly decrease secreted Aß in neurons, suggesting that internalized somatodendritic APP may not constitute a major source of Aß. Interestingly, like APP, somatodendritic low-density lipoprotein receptor (LDLR) internalization does not require its CME motif. These results highlight intriguing differences in neuronal internalization pathways and refine our understanding of Aß production and secretion.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Precursor de Proteína beta-Amiloide
/
Doença de Alzheimer
Limite:
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2023
Tipo de documento:
Article