Two-pore Channels Pair Up♦

♦ See referenced article, J. Biol. Chem. 2011, 286, 37058–37062

Two-pore channels (TPCs) are receptor complexes that have been recently discovered to release Ca²⁺ in response to NAADP, a potent Ca²⁺-mobilizing agent. Humans express two of the three known TPC isoforms: TPC1 and TPC2. These channels are found in the endolysosomal system, but how they interact with one another to produce gateways for ions is unclear. In this Paper of the Week, Antony Galione and colleagues at Oxford University in the United Kingdom demonstrate that TPC1 and TPC2 form homo- and heteromeric complexes by interacting in a head-to-tail symmetry. The authors suggest that the homo- and heteromeric complexes differ in their functions, such as Ca²⁺ signaling and mediating endolysosomal fusion events.

Human TPCs form homo- and heteromeric complexes.