title: Analysis of the amyloid precursor protein role in neuritogenesis reveals a biphasic SH-SY5Y neuronal cell differentiation model.
abstract: The existence of an intrinsic programme controlling neuritogenesis and activated during early neuronal differentiation and regeneration stages is well established. However, the identity and role of each molecular player and event, as well as how such a programme is modified by environmental signals, remain a focus of research. The amyloid precursor protein (APP) is a neuromodulator of the developing and mature nervous system, although in a highly complex manner which is far from clear. To study APP-induced neuritogenesis, the retinoic acid (RA)-induced SH-SY5Y cell differentiation model was first minutely characterized in terms of RA dose, morphological outputs and relevant biochemical markers. The findings reported here unveiled two differentiation phases for the 10 μM RA dose: 1-4 (4 days excluded) and 4-8 days, clearly defined by fold increases in the ratio between APP and acetylated Tubulin. Moreover, we describe, for the first time, a unique peak of secreted APP (sAPP)/APP ratio in the first phase. Subsequent APP and sAPP modulations confirmed that a high sAPP/APP ratio potentiates the elongation of smaller processes at the earlier neuritogenic phase. This sAPP/APP ratio drops in the second phase, as holoAPP levels increase to assist the maintenance of the longer neurites, potentially via their stabilization.
authors.affiliation: Laboratório de Neurociências e Sinalização Celular, CBC and iBiMED, Secção Autónoma de Ciências da Saúde, Universidade de Aveiro, Aveiro, Portugal.
authors.forename: Joana Fernandes
authors.initials: JF
authors.lastname: da Rocha
authors.affiliation: Laboratório de Neurociências e Sinalização Celular, CBC and iBiMED, Secção Autónoma de Ciências da Saúde, Universidade de Aveiro, Aveiro, Portugal.
authors.forename: Odete A B
authors.initials: OA
authors.lastname: da Cruz e Silva
authors.affiliation: Laboratório de Neurociências e Sinalização Celular, CBC and iBiMED, Secção Autónoma de Ciências da Saúde, Universidade de Aveiro, Aveiro, Portugal.
authors.forename: Sandra Isabel
authors.initials: SI
authors.lastname: Vieira
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D016564:Amyloid beta-Protein Precursor; D014212:Tretinoin
keywords: acetylated tubulin; amyloid precursor protein; morphometric analysis; neurite outgrowth; neuritogenesis; neuroblastoma cells