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Increased processing of APLP2 and APP with concomitant formation of APP intracellular domains in BDNF and retinoic acid‐differentiated human neuroblastoma cells
Author(s) -
Holback Sofia,
Adlerz Linda,
Iverfeldt Kerstin
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03440.x
Subject(s) - amyloid precursor protein , tropomyosin receptor kinase b , retinoic acid , endocrinology , medicine , neurotrophic factors , brain derived neurotrophic factor , biology , intracellular , alpha secretase , neurotrophin , neuroblastoma , chemistry , microbiology and biotechnology , receptor , biochemistry , cell culture , alzheimer's disease , gene , genetics , disease
The amyloid precursor protein (APP) belongs to a conserved gene family, also including the amyloid precursor‐like proteins, APLP1 and APLP2. We have previously shown that all members of the APP protein family are up‐regulated upon retinoic acid (RA)‐induced neuronal differentiation of SH‐SY5Y neuroblastoma cells. Here, we demonstrate that RA also affects the processing of APLP2 and APP, as shown by increased shedding of both sAPLP2 and sAPPα, as well as elevated levels of the APP intracellular domains (AICDs). Brain‐derived neurotrophic factor (BDNF) has been reported to induce APP promoter activity and RA induces expression of the tyrosine kinase receptor B (TrkB) in neuroblastoma cells. We show that the increase in shedding of both APLP2 and APP in response to RA is not mediated through the TrkB receptor. However, BDNF concomitant with RA increased the expression of APP even further. In addition, the secretion of sAPLP2 and sAPPα as well as the levels of AICDs were increased in response to BDNF. In contrast, the levels of membrane‐bound APP C‐terminal fragment C99 significantly decreased. Our results suggest that RA and BDNF shifts APP processing towards the α‐secretase pathway. In addition, we show that RA and BDNF regulate N ‐linked glycosylation of APLP1.