APP/Go signaling modulates the interaction between APP and BACE1

ANTONINO, MAGDALENA; BIGNANTE, ANAHÍ; MARMO, PAULA; ALFREDO, LORENZO

Carlos Paz

Congreso; XXXIV Reunión Anual SAN 2019; 2019

Sociedad Argentina de Investigación en Neurociencias (SAN)

The amyloid beta (Aβ) deposition in the brain has a key role in the etiology of Alzheimer´s disease. The encounter of amyloid precursor protein (APP) and BACE1 is the most critical event in amyloidogenesis. The factors modulating this event are poorly understood but there is crescent evidence about the importance of endosomal sorting of both proteins. Also, some evidence suggests that Aβ is capable of induces its own production in a feed-forward fashion, but the mechanism is yet unclear. We hypotetized that this mechanism implies a change in the intracellular distribution of APP and BACE1, and that depends on Aβ interaction with APP and its signaling pathway mediates by Go/βγ. We found that treatment with Aβ was able to increase the colocalization of APP and BACE1, in soma and processes of hippocampal neurons. This effect was avoided by a pretreatment with gallein, an inhibitor of βγ complex. Also, we found that this increase occurred in recycling endosomes as both proteins incremented its colocalization with Rab11. Moreover, overexpressing a system of bimolecular fluorescence complementation (APP-Vn /BACE1-Vc) we found an increase in the degree of interaction between both proteins in N2A cell cultures induced by both, oligomeric and fibrilar Aβ. This effect was avoided by a pretreatment with gallein. In conclusion, Aβ induces an increment in the colocalization and interaction of APP and BACE1 in recycling endosomes which is dependent of Go/βγ signalling.