FE65 proteins regulate NMDA receptor activation-induced amyloid precursor protein processing.
作者： Jaehong Suh , Alvin Lyckman , Lirong Wang , Elizabeth A. Eckman , Suzanne Y. Guénette
DOI: 10.1111/J.1471-4159.2011.07419.X
关键词: Nuclear protein 、 Amyloid precursor protein 、 NMDA receptor 、 Biology 、 Secretion 、 Protein family 、 Calpain 、 Phosphorylation 、 APLP2 、 Biochemistry
摘要: Amyloid precursor protein (APP) family members and their proteolytic products are implicated in normal nervous system function Alzheimer's disease pathogenesis. APP processing Aβ secretion regulated by neuronal activity. Various data suggest that NMDA receptor (NMDAR) activity plays a role both non-amyloidogenic amyloidogenic depending on whether synaptic or extrasynaptic NMDARs activated, respectively. The APP-interacting FE65 proteins modulate trafficking cell lines, but little is known about contribution to neurons, either vivo vitro. In this study, we examined the of WT FE65/FE65L1 double knockout neurons under basal conditions following NMDAR activation. We report facilitate without affecting fast axonal transport pre-synaptic terminals. addition, an NMDAR-dependent pathway. Generation high-molecular weight (HMW) species bearing C-terminal epitope was also observed These HMW require proteasomal calpain activities for accumulation. Recovery polypeptide fragments from electroeluted having molecular weights consistent with I cleavage suggests complexes formed metabolic products. Our results indicate contribute physiological accumulation resulting
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