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In Focus: Two Pore Segment Channels (TPCs)

Among various vertebrate species, three genes are known to encode two pore segment channels (TPCs) termed TPC1-3. Interestingly, TPC3 seems to be absent from the genomes of primates and rodents9. The primary sequence of these channels indicates the presence of two putative pore-forming repeats. Each repeat contains six transmembrane domains and a pore loop, a structure strikingly reminiscent of many voltage-gated Na+ (NaV) and Ca2+ (CaV) channels6. These twelve transmembrane structures are further thought to form functional dimers5. Both TPC1 and TPC2 show ubiquitous expression, while that of TPC1 is exceptionally high in spleen, lung, liver, and kidney6.

Ca2+-mobilizing messengers such as inositol triphosphate, cyclic ADP ribose and nicotinic acid adenosine dinucleotide phosphate (NAADP) are responsible for the intracellular changes in Ca2+ ion concentration1. In contrast to the other Ca2+-mobilizing agents, NAADP, the most potent of these Ca2+ releasing molecules increases the cytosolic Ca2+ concentration via Ca2+ channels located on acidic vesicles (endolysosomes)4,7. Only quite recently, after almost a decade of being cloned, TPC1 and TPC2 were both found to be responsible for the NAADP-induced release of Ca2+ 2,3. Evidence that these two channels are indeed responsible for the release of Ca2+ is quite compelling since overexpression of TPC1 and its knockdown or point mutation of a critical residue increases and exacerbates Ca2+ release respectively2. In addition, b-cells from TPC2 knockout mice exhibited no Ca2+ release from endolysosomes upon NAADP stimulation3. Finally, in a study using immunopurified channels, it was demonstrated that TPC1 and TPC2 both respond to very low concentrations of NAADP and are unequivocally responsible for the release of Ca2+, whereas TPC3 may negatively regulate the release of Ca2+ 8.

As these channels have only recently been discovered, very little is known about their physiology and gating mechanisms. Their probable involvement in a number of diseases such as lysosomal storage disease (LSDs), caused by the dysfunction of lysosomal associated proteins, has yet to be deciphered9.

Alomone Labs is pleased to offer highly specific antibodies against TPC1 and TPC2. Anti-TPCN1 Antibody (#ACC-071) and Anti-TPCN2 Antibody (#ACC-072) can be used in western blot analysis and/or immunohistochemistry.


  1. Bruzzone, R. et al. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 13644.
  2. Chew, S.S. et al. (2010) Exp. Neurol. 225, 250.
  3. Falk, MM. (2000) Eur. J. Cell. Biol. 79, 564.
  4. Goodenough, D.A. and Paul, D.L. (2011) Cold Spring Harb. Persp. Biol. 2009, 1.
  5. Hu, X. et al. (2006) Biophys. J. 90, 140.
  6. Litvin, O. et al. (2006) J. Cell. Mol. Med. 10, 613.
  7. Nakagawa, S. et al. (2010) Curr. Opin. Struct. Biol. 20, 423.
  8. Panchin, Y.V. (2005) J. Exp. Biol. 208, 1415.
  9. Trexter, E.B. et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 5836.
  10. Shestopalov, V.I. and Panchin, Y. (2008) Cell. Mol. Life Sci. 65, 376.
  11. Tang, Q. et al. (2009) J. Gen. Physiol. 133, 555.
  12. Unger, V.M. et al. (1999) Science 283, 1176.