APP/Go signaling modulates the interaction between APP and BACE1

ANTONINO, MAGDALENA; MARMO, PAULA ; ALFREDO LORENZO; BIGNANTE, ELENA A.

Cordoba

Congreso; XXXIV Annual Meeting of the Sociedad Argentina de Investigación en Neurociencia (SAN); 2019

Sociedad Argentina de Investigación en Neurociencia (SAN)

Cellular and Molecular NeurobiologyP23.-APP/Go signaling modulates the interaction betweenAPP and BACE1Magdalena Antonino1, Paula Marmo1, Alfredo Lorenzo1, Anahi Bignante11 INIMEC-CONICET-UNC, 2 IFEC-CONICET, 3IUCBC, 4Presenting author: Elena Anahi Bignante, abignante@immf.uncor.edu__________________________________________________________________________The amyloid beta (Aβ) deposition in the brain has a key role in the etiology ofAlzheimer´s disease. The encounter of amyloid precursor protein (APP) andBACE1 is the most critical event in amyloidogenesis. The factors modulating thisevent are poorly understood but there is crescent evidence about the importanceof endosomal sorting of both proteins. Also, some evidence suggests that Aβ iscapable of induces its own production in a feed-forward fashion, but themechanism is yet unclear. We hypotetized that this mechanism implies a change inthe intracellular distribution of APP and BACE1, and that depends on Aβinteraction with APP and its signaling pathway mediates by Go/βγ. We found thattreatment with Aβ was able to increase the colocalization of APP and BACE1, insoma and processes of hippocampal neurons. This effect was avoided by apretreatment with gallein, an inhibitor of βγ complex. Also, we found that thisincrease occurred in recycling endosomes as both proteins incremented itscolocalization with Rab11. Moreover, overexpressing a system of bimolecularfluorescence complementation (APP-Vn /BACE1-Vc) we found an increase in thedegree 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. Inconclusion, Aβ induces an increment in the colocalization and interaction of APPand BACE1 in recycling endosomes which is dependent of Go/βγ signalling.