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Two-pore channels (TPCs): current controversies.

Anthony J Morgan1, Antony Galione

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Summary
This summary is machine-generated.

Two-pore channels (TPCs) may not directly bind nicotinic acid adenine dinucleotide phosphate (NAADP). Emerging evidence suggests TPCs are sodium channels regulated by lipids and ATP, complicating their role in cellular calcium signaling.

Keywords:
Ca2+NAADPTPCchannellysosome

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Area of Science:

  • Cell Biology
  • Molecular Physiology
  • Ion Channel Function

Background:

  • Two-pore channels (TPCs) were proposed as targets for the calcium (Ca2+)-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP).
  • This hypothesis suggested TPCs mediate NAADP-dependent calcium release from endo-lysosomal stores.

Purpose of the Study:

  • To critically evaluate the evidence linking TPCs to NAADP signaling.
  • To discuss the implications of recent findings on TPC function within the context of endo-lysosomal calcium signaling.

Main Methods:

  • Literature review and critical analysis of existing research on TPCs and NAADP.
  • Comparison of proposed TPC functions with established models of endo-lysosomal calcium regulation.

Main Results:

  • Evidence suggests NAADP may not directly bind TPCs, potentially requiring accessory proteins.
  • Recent studies propose TPCs function as selective sodium (Na+) channels, regulated by phosphatidylinositol 3,5-bisphosphate and ATP, challenging their role as Ca2+ channels.

Conclusions:

  • The role of TPCs in NAADP signaling is more complex than initially thought.
  • Alternative mechanisms for TPC regulation and function, particularly as Na+ channels, need further investigation to understand their contribution to cellular calcium homeostasis.