Gain-of-function mutations in the MEC-4 DEG/ENaC sensory mechanotransduction channel alter gating and drug blockade

Journal of General Physiology

Volumn 129, Issue 2, 2007, Pages 161-173

  Brown, Austin L ^a   Fernandez Illescas, Silvia M ^a   Liao, Zhiwen ^a   Goodman, Miriam B ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMILORIDE; BENZAMIL; CYSTEINE; ION CHANNEL; PROTEIN ENAC; PROTEIN MEC 10; PROTEIN MEC 4; SODIUM CHANNEL; UNCLASSIFIED DRUG;

ALLELE; ANIMAL CELL; ARTICLE; CAENORHABDITIS ELEGANS; CHANNEL GATING; CONTROLLED STUDY; DRUG INHIBITION; MECHANICAL STIMULATION; MEMBRANE PERMEABILITY; MUTATION; NONHUMAN; OOCYTE; PROTEIN DOMAIN; SENSATION; SIGNAL TRANSDUCTION; VOLTAGE CLAMP;

AMILORIDE; AMINO ACID SEQUENCE; ANIMALS; CAENORHABDITIS ELEGANS PROTEINS; DOSE-RESPONSE RELATIONSHIP, DRUG; EPITHELIAL SODIUM CHANNEL; ION CHANNEL GATING; MECHANOTRANSDUCTION, CELLULAR; MEMBRANE POTENTIALS; MEMBRANE PROTEINS; MICROINJECTIONS; MODELS, BIOLOGICAL; MOLECULAR SEQUENCE DATA; MUTATION; OOCYTES; PATCH-CLAMP TECHNIQUES; PROTEIN CONFORMATION; PROTEIN SUBUNITS; SODIUM CHANNEL BLOCKERS; SODIUM CHANNELS; XENOPUS LAEVIS;

EID: 33846592854     PISSN: 00221295     EISSN: 00221295     Source Type: Journal    
DOI: 10.1085/jgp.200609672     Document Type: Article

References (35)

1. + channel 1 by inducing a conformational change that exposes a residue associated with neurodegeneration. J. Biol. Chem. 273:30204-30207.
2. Bass, R.B., P. Strop, M. Barclay, and D.C. Rees. 2002. Crystal structure of Escherichia coli MscS, a voltage-modulated and mechanosensitive channel. Science. 298:1582-1587.
3. Bateman, A., L. Coin, R. Durbin, R.D. Finn, V. Hollich, S. Griffiths-Jones, A. Khanna, M. Marshall, S. Moxon, E.L. Sonnhammer, et al. 2004. The Pfam protein families database. Nucleic Acids Res. 32:D138-D141.
4. + channel is made of three homologous subunits. Nature. 367:463-467.
5. Chalfie, M., and E. Wolinsky. 1990. The identification and suppression of inherited neurodegeneration in Caenorhabditis elegans. Nature. 345:410-416.
6. Chang, G., R.H. Spencer, A.T. Lee, M.T. Barclay, and D.C. Rees. 1998. Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel. Science. 282:2220-2226.
7. Choudhary, G., M. Yotsu-Yamashita, L. Shang, T. Yasumoto, and S.C. Dudley Jr. 2003. Interactions of the C-11 hydroxyl of tetrodotoxin with the sodium channel outer vestibule. Biophys. J. 84:287-294.
8. Driscoll, M., and M. Chalfie. 1991. The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration. Nature. 349:588-593.
9. Garty, H., and L.G. Palmer. 1997. Epithelial sodium channels: function, structure, and regulation. Physiol. Rev. 77:359-396.
10. Gillespie, J.I. 1983. The distribution of small ions during the early development of Xenopus laevis and Ambystoma mexicanum embryos. J. Physiol. 344:359-377.
11. Goodman, M.B., G.G. Ernstrom, D.S. Chelur, R. O'Hagan, C.A. Yao, and M. Chalfie. 2002. MEC-2 regulates C. elegans DEG/ENaC channels needed for mechanosensation. Nature. 415:1039-1042.
12. Green, W.N., and O.S. Andersen. 1991. Surface charges and ion channel function. Annu. Rev. Physiol. 53:341-359.
13. + channel pore through mutant cycles with a peptide inhibitor. Science. 268:307-310.
14. Hille, B. 2001. Ion Channels of Excitable Membranes. Third edition. Sinauer Associates, Inc., Sunderland, MA. 814 pp.
15. Hong, K., I. Mano, and M. Driscoll. 2000. In vivo structure-function analyses of Caenorhabditis elegans MEC-4, a candidate mechanosensory ion channel subunit. J. Neurosci. 20:2575-2588.
16. Huang, M., and M. Chalfie. 1994. Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans. Nature. 367:467-470.
17. A receptor. J. Neurosci. 18:8590-8604.
18. Kash, T.L., A. Jenkins, J.C. Kelley, J.R. Trudell, and N.L. Harrison. 2003. Coupling of agonist binding to channel gating in the GABA(A) receptor. Nature. 421:272-275.
19. + channel ENaC. J. Physiol. 543:413-424.
20. + channel ENaC outer pore disrupt amiloride block by increasing its dissociation rate. Mol. Pharmacol. 64:848-856.
21. Kellenberger, S., and L. Schild. 2002. Epithelial sodium channel/ degenerin family of ion channels: a variety of functions for a shared structure. Physiol. Rev. 82:735-767.
22. Ladbury, J.E. 1996. Just add water! The effect of water on the specificity of protein-ligand binding sites and its potential application to drug design. Chem. Biol. 3:973-980.
23. Lai, C.-C., K. Hong, M. Kinnell, M. Chalfie, and M. Driscoll. 1996. Sequence and transmembrane topology of MEC-4, an ion channel subunit required for mechanotransduction in Caenorhabditis elegans. J. Cell Biol. 133:1071-1081.
24. McNicholas, C.M., and C.M. Canessa. 1997. Diversity of channels generated by different combinations of epithelial sodium channel subunits. J. Gen. Physiol. 109:681-692.
25. O'Hagan, R., M. Chalfie, and M.B. Goodman. 2005. The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals. Nat. Neurosci. 8:43-50.
26. Palmer, L.G. 1990. Epithelial Na channels: the nature of the conducting pore. Ren. Physiol. Biochem. 13:51-58.
27. Palmer, L.G., and G. Frindt. 1986. Amiloride-sensitive Na channels from the apical membrane of the rat cortical collecting tubule. Proc. Natl. Acad. Sci. USA. 83:2767-2770.
28. Rabito, C.A., C.A. Rotunno, and M. Cereijido. 1978. Amiloride and calcium effect on the outer barrier of the frog skin. J. Membr. Biol. 42:169-187.
29. Royal, D.C., L. Bianchi, M.A. Royal, M. Lizzio Jr., G. Mukherjee, Y.O. Nunez, and M. Driscoll. 2005. Temperature-sensitive mutant of the Caenorhabditis elegans neurotoxic MEC-4(d) DEG/ENaC channel identifies a site required for trafficking or surface maintenance. J. Biol. Chem. 280:41976-41986.
30. Schild, L., E. Schneeberger, I. Gautschi, and D. Firsov. 1997. Identification of amino acid residues in the α, β, and γ subunits of the epithelial sodium channel (ENaC) involved in amiloride block and ion permeation. J. Gen. Physiol. 109:15-26.
31. Schreiber, G., and A.R. Fersht. 1995. Energetics of protein-protein interactions: analysis of the barnase-barstar interface by single mutations and double mutant cycles. J. Mol. Biol. 248:478-486.
32. Snyder, P.M., D.B. Bucher, and D.R. Olson. 2000. Gating induces a conformational change in the outer vestibule of ENaC. J. Gen. Physiol. 116:781-790.
33. Vassalli, J.D., and D. Belin. 1987. Amiloride selectively inhibits the urokinase-type plasminogen activator. FEBS Lett. 214:187-191.
34. Woodhull, A.M. 1973. Ionic blockage of sodium channels in nerve. J. Gen. Physiol. 61:687-708.
35. Zeslawska, E., A. Schweinitz, A. Karcher, P. Sondermann, S. Sperl, J. Sturzebecher, and U. Jacob. 2000. Crystals of the urokinase type plasminogen activator variant βc-uPA in complex with small molecule inhibitors open the way towards structure-based drug design. J. Mol. Biol. 301:465-475.