Distinct anterograde trafficking pathways of BACE1 and amyloid precursor protein from the TGN and the regulation of amyloid-ß production.
Mol Biol Cell
; 31(1): 27-44, 2020 01 01.
Article
em En
| MEDLINE
| ID: mdl-31746668
ABSTRACT
Processing of amyloid precursor protein (APP) by the ß-secretase BACE1 is the initial step of the amyloidogenic pathway to generate amyloid-ß (Aß). Although newly synthesized BACE1 and APP are transported along the secretory pathway, it is not known whether BACE1 and APP share the same post-Golgi trafficking pathways or are partitioned into different transport routes. Here we demonstrate that BACE1 exits the Golgi in HeLa cells and primary neurons by a pathway distinct from the trafficking pathway for APP. By using the Retention Using Selective Hooks system, we show that BACE1 is transported from the trans-Golgi network to the plasma membrane in an AP-1- and Arf1/4-dependent manner. Subsequently, BACE1 is endocytosed to early and recycling endosomes. Perturbation of BACE1 post-Golgi trafficking results in an increase in BACE1 cleavage of APP and increased production of both Aß40 and Aß42. These findings reveal that Golgi exit of BACE1 and APP in primary neurons is tightly regulated, resulting in their segregation along different transport routes, which limits APP processing.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Aspártico Endopeptidases
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Precursor de Proteína beta-Amiloide
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Transporte Proteico
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Secretases da Proteína Precursora do Amiloide
Limite:
Humans
Idioma:
En
Revista:
Mol Biol Cell
Ano de publicação:
2020
Tipo de documento:
Article