Distinct anterograde trafficking pathways of BACE1 and amyloid precursor protein from the TGN and the regulation of amyloid-beta production
Jing Zhi A Tan, Lou Fourriere, Jingqi Wang, Franck Perez, Gaelle Boncompain, Paul A Gleeson
Molecular Biology of the Cell | AMER SOC CELL BIOLOGY | Published : 2020
Processing of amyloid precursor protein (APP) by the β-secretase, BACE1, is the initial step of the amyloidogenic pathway to generate amyloid-β (Aβ). Although newly synthesised BACE1 and APP are transported along the secretory pathway, it is not known if 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. Using the RUSH system, we show that BACE1 is transported from the TGN to the plasma membrane in an AP-1 and Arf1/4 dependent manner. Subsequently, BACE1 is endocytosed to early and recycling ..View full abstract
Awarded by National Health and Medical Research Council of Australia
Confocal microscopy was performed at the Biological Optical Microscopy Platform (BOMP) at the University of Melbourne. This work was supported by funding from the National Health and Medical Research Council of Australia (APP1163862). J.Z.A.T. and J.W. are supported by University of Melbourne International Postgraduate Awards. We gratefully acknowledge Fiona Houghton for reagents and expert technical advice, Wei Hong Toh and other members of the Gleeson laboratory for valuable discussions, Allison Van De Meene for maintenance of the spinning disk, and Ellie Cho for help with the quantitation.