Effect of NAADP in autophagic signaling regulated by mTOR (mammalian Target of Rapamycin) in astrocytes

Abstract

Autophagy is a catabolic process essential for the turnover of cytosolic proteins and organelles. It involves the formation of a double membrane structure known as the autophagosome around a targeted region of the cytosol. The Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+ mobilizing messenger that in many cells releases Ca2+ from the endo-lysosomal system, this effect is mediated by the two-pore channels (TPCs), especially TPC type 2. Whether NAADP acts as a messenger in astrocytes is unclear and the functions on autophagy have yet to be defined. In our present work, the effects of NAADP and the relationship of this event in autophagy regulation with the mTOR pathway remains to be studied. Several evidences provide that NAADP-evoked Ca2+ signals might regulate autophagy on the first (by mTOR pathway) and the last step (by p62 modulation). Therefore, the objective of this work is to investigate the autophagic intracellular pathways mediated by NAADP in murine astrocytes, and the possible interrelationship with mTOR via. For this purpose, we will evaluate autophagy modulation by confocal microscopy, flow cytometer and the expression of genes and proteins related to these pathways, which will be analyzed by molecular biology techniques. (AU)