title: Nicotinic acid adenine dinucleotide phosphate (NAADP) regulates autophagy in cultured astrocytes.
abstract: Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca(2+)-mobilizing messenger that in many cells releases Ca(2+) from the endolysosomal system. Recent studies have shown that NAADP-induced Ca(2+) mobilization is mediated by the two-pore channels (TPCs). Whether NAADP acts as a messenger in astrocytes is unclear, and downstream functional consequences have yet to be defined. Here, we show that intracellular delivery of NAADP evokes Ca(2+) signals from acidic organelles in rat astrocytes and that these signals are potentiated upon overexpression of TPCs. We also show that NAADP increases acidic vesicular organelle formation and levels of the autophagic markers, LC3II and beclin-1. NAADP-mediated increases in LC3II levels were reduced in cells expressing a dominant-negative TPC2 construct. Our data provide evidence that NAADP-evoked Ca(2+) signals mediated by TPCs regulate autophagy.
authors: From the Department of Pharmacology, Federal University of São Paulo, São Paulo SP 04044-020, Brazil.
authors: Gustavo J S
authors: GJ
authors: Pereira
authors: Hanako
authors: H
authors: Hirata
authors: Gian M
authors: GM
authors: Fimia
authors: Lúcia G
authors: LG
authors: do Carmo
authors: Claudia
authors: C
authors: Bincoletto
authors: Sang W
authors: SW
authors: Han
authors: Roberta S
authors: RS
authors: Stilhano
authors: Rodrigo P
authors: RP
authors: Ureshino
authors: Duncan
authors: D
authors: Bloor-Young
authors: Grant
authors: G
authors: Churchill
authors: Mauro
authors: M
authors: Piacentini
authors: Sandip
authors: S
authors: Patel
authors: Soraya S
authors: SS
authors: Smaili
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