NAADP/TPC2/Ca(2+) Signaling Inhibits Autophagy
Yingying Lu1, Baixia Hao1, Richard Graeff1
1Department of Physiology; University of Hong Kong; Hong Kong, PR China.
Communicative & Integrative Biology
|April 23, 2014
Summary
Nicotinic adenine acid dinucleotide phosphate (NAADP) mobilizes calcium from lysosomes, a process involving TPC2 channels. This signaling pathway regulates autophagic flux and neural differentiation in mouse stem cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Neuroscience
Background:
- Nicotinic adenine acid dinucleotide phosphate (NAADP) is a potent calcium (Ca2+) mobilizing messenger.
- NAADP releases Ca2+ from acidic lysosome-related stores, amplifying into global Ca2+ waves via CICR.
- Two pore channel 2 (TPC2) is identified as the NAADP receptor, a voltage-gated ion channel.
Purpose of the Study:
- To elucidate the mechanism by which NAADP-induced Ca2+ release elevates lysosomal pH.
- To investigate the role of TPC2 in the neural differentiation of mouse embryonic stem (ES) cells.
Main Methods:
- Investigating the signaling pathway of NAADP/TPC2/Ca2+.
- Analyzing the effect of TPC2 on lysosomal pH and autophagic flux.
- Examining TPC2 expression during neural differentiation of mouse ES cells.
Main Results:
- NAADP/TPC2/Ca2+ signaling inhibits autophagosome-lysosome fusion by increasing lysosomal pH, thus arresting autophagic flux.
- TPC2 is downregulated during mouse ES cell neural differentiation.
- TPC2 downregulation facilitates neural lineage entry in mouse ES cells.
Conclusions:
- NAADP-induced Ca2+ release via TPC2 increases lysosomal pH, impacting cellular processes like autophagy.
- TPC2 plays a crucial role in regulating neural differentiation of mouse ES cells, with its downregulation being permissive for this process.
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