Patch-clamp technique to characterize ion channels in enlarged individual endolysosomes

Cang, C. et al. mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state. Cell 4, 778–790 (2013).

Dong, X.P. et al. The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature 455, 992–996 (2008).

Cang, C. et al. TMEM175 is an organelle K(+) channel regulating lysosomal function. Cell 5, 1101–1112 (2015).

Dong, X.P. et al. PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca(2+) release channels in the endolysosome. Nat. Commun. 1, 38 (2010).

Jentsch, T.J. et al. CLC chloride channels and transporters. Curr. Opin. Neurobiol. 3, 319–325 (2005).

Grimm, C. et al. Role of TRPML and two-pore channels in endolysosomal cation homeostasis. J. Pharmacol. Exp. Ther. 2, 236–244 (2012).

Grimm, C. et al. High susceptibility to fatty liver disease in two-pore channel 2-deficient mice. Nat. Commun. 5, 4699 (2014).

Sakurai, Y. et al. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. Science 6225, 995–998 (2015).

Chen, C.C. et al. A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV. Nat. Commun. 5, 4681 (2014).

Xu, H. & Ren, D. Lysosomal physiology. Annu. Rev. Physiol. 77, 57–80 (2015).

Hockey, L.N. et al. Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition. J. Cell Sci. 128, 232–238 (2015).

Schwake, M. et al. Lysosomal membrane proteins and their central role in physiology. Traffic 7, 739–748 (2013).

Chapel, A. et al. An extended proteome map of the lysosomal membrane reveals novel potential transporters. Mol. Cell Proteomics. 6, 1572–1588 (2013).

Zhang, F. & Li, P.-L. Reconstitution and characterization of a nicotinic acid adenine dinucleotide phosphate (NAADP)-sensitive Ca2+ release channel from liver lysosomes of rats. J. Biol. Chem. 282, 25259–25269 (2007).

Zhang, F. et al. TRP-ML1 functions as a lysosomal NAADP-sensitive Ca2+ release channel in coronary arterial myocytes. J. Cell. Mol. Med. 13, 3174–3185 (2009).

Pitt, S.J. et al. TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+. J. Biol. Chem. 285, 35039–35046 (2010).

Pitt, S.J. et al. Reconstituted human TPC1 is a proton-permeable ion channel and is activated by NAADP or Ca2+. Sci. Signal. 7, ra46 (2014).

Patel, S. Function and dysfunction of two-pore channels. Sci. Signal. 8, re7 (2015).

Feijóo-Bandín, S. et al. Two-pore channels (TPCs): novel voltage-gated ion channels with pleiotropic functions. Channels 20, 1–14 (2016).

Grimm, C. et al. Role of TRPML and two-pore channels in endolysosomal cation homeostasis. J. Pharmacol. Exp. Ther. 342, 236–244 (2012).

Venkatachalam, K. et al. The role of TRPMLs in endolysosomal trafficking and function. Cell Calcium 58, 48–56 (2015).

Cheng, X. et al. Mucolipins: intracellular TRPML1-3 channels. FEBS Lett. 584, 2013–2021 (2010).

Schieder, M. et al. Planar patch clamp approach to characterize ionic currents from intact lysosomes. Sci. Signal. 151, 13 (2010).

Jha, A. et al. Convergent regulation of the lysosomal two-pore channel-2 by Mg2+, NAADP, PI(3,5)P2 and multiple protein kinases. EMBO J. 33, 501–511 (2014).

Samie, M. et al. A TRP channel in the lysosome regulates large particle phagocytosis via focal exocytosis. Dev Cell. 26, 511–524 (2013).

Bellono, N.W. et al. A melanosomal two-pore sodium channel regulates pigmentation. Sci. Rep. 6, 26570 (2016).

Shen, J. et al. SNARE bundle and syntaxin N-peptide constitute a minimal complement for Munc18-1 activation of membrane fusion. J. Cell Biol. 190, 55–63 (2010).

Brailoiu, E. et al. An NAADP-gated two-pore channel targeted to the plasma membrane uncouples triggering from amplifying Ca2+ signals. J. Biol. Chem. 285, 38511–38516 (2010).

Cerny, J. et al. The small chemical vacuolin-1 inhibits Ca(2+)-dependent lysosomal exocytosis but not cell resealing. EMBO Rep. 5, 883–888 (2004).

Axon Instruments The Axon Guide for Electrophysiology & Biophysics Laboratory Techniques http://www.psychiatry.wustl.edu/zorumski/Axon_Guide.PDF (1993).

Cummins, T.R. et al. Voltage-clamp and current-clamp recordings from mammalian DRG neurons. Nat. Protoc. 4, 1103–1112 (2009).

Guo, H. et al. Role of TRPM in melanocytes and melanoma. Exp. Dermatol. 21, 650–654 (2012).

Lange, I. et al. TRPM2 functions as a lysosomal Ca2+-release channel in beta cells. Sci. Signal. 2, ra23 (2009).

Nilius, B. et al. Transient receptor potential cation channels in disease. Physiol. Rev. 87, 165–217 (2006).

Miao, Y. et al. A TRP channel senses lysosome neutralization by pathogens to trigger their expulsion. Cell 6, 1306–1319 (2015).

Gu, M. & Xu, H. A painful TR(i)P to lysosomes. J. Cell Biol. 215, 309–312 (2016).

Dong, X.P. et al. TRP channels of intracellular membranes. J. Neurochem. 113, 313–328 (2010).

Cang, C. et al. The voltage-gated sodium channel TPC1 confers endolysosomal excitability. Nat. Chem. Biol. 10, 463–469 (2014).

Melchionda, M. et al. Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo. J. Cell. Biol. 212, 803–813 (2016).

Wang, X. et al. TPC proteins are phosphoinositide-activated sodium-selective ion channels in endosomes and lysosomes. Cell 2, 372–383 (2012).

Novarino, G. et al. Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis. Science 5984, 1398–1401 (2010).

Huang, P. et al. P2X4 forms functional ATP-activated cation channels on lysosomal membranes regulated by luminal pH. J. Biol. Chem. 289, 17658–17667 (2014).

Cao, Q. et al. BK channels alleviate lysosomal storage diseases by providing positive feedback regulation of lysosomal Ca2+ release. Dev. Cell 4, 427–441 (2015).

Bertl, A. et al. Electrical measurements on endomembranes. Science 258, 873–874 (1992).