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.


Autore Pugliese

Tutti gli autori

  • Pereira G.J.S. , Hirata H. , Fimia G.M. , do Carmo L.G. , Bincoletto C. , Han S.W. , Stilhano R.S. , Ureshino R.P. , Bloor-Young D. , Churchill G. , Piacentini M. , Patel S. , Smaili S.S.

Titolo volume/Rivista

JOURNAL OF BIOLOGICAL CHEMISTRY


Anno di pubblicazione

2011

ISSN

1083-351X

ISBN

Non Disponibile


Numero di citazioni Wos

50

Ultimo Aggiornamento Citazioni

25/04/2018


Numero di citazioni Scopus

52

Ultimo Aggiornamento Citazioni

26/04/2018


Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile