Reciprocal modulation between amyloid precursor protein and synaptic membrane cholesterol revealed by live cell imaging.

ABSTRACT: The amyloid precursor protein (APP) has been extensively studied because of its association with Alzheimer's disease (AD). However, APP distribution across different subcellular membrane compartments and its function in neurons remains unclear. We generated an APP fusion protein with a pH-sensitive green fluorescent protein at its ectodomain and a pH-insensitive blue fluorescent protein at its cytosolic domain and used it to measure APP's distribution, subcellular trafficking, and cleavage in live neurons. This reporter, closely resembling endogenous APP, revealed only a limited correlation between synaptic activities and APP trafficking. However, the synaptic surface fraction of APP was increased by a reduction in membrane cholesterol levels, a phenomenon that involves APP's cholesterol-b

SUBMITTER: DelBove CE 

PROVIDER: S-EPMC6588454 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature