The nematode degenerin UNC-105 forms ion channels that are activated by degeneration- or hypercontraction-causing mutations

Jaime García-Añoveros, Jesus A. García, Jing Dong Liu, David P. Corey*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Nematode degenerins have been implicated in touch sensitivity and other forms of mechanosensation. Certain mutations in several degenerin genes cause the swelling, vacuolation, and death of neurons, and other mutations in the muscle degenerin gene unc-105 cause hypercontraction. Here, we confirm that unc-105 encodes an ion channel and show that it is constitutively active when mutated. These mutations disrupt different regions of the channel and have different effects on its gating. The UNC-105 channels are permeable to small monovalent cations but show voltage-dependent block by Ca2+ and Mg2+. Amiloride also produces voltage-dependent block, consistent with a single binding site 65% into the electric field. Mammalian cells expressing the mutant channels accumulate membranous whorls and multicompartment vacuoles, hallmarks of degenerin-induced cell death across species.

Original languageEnglish (US)
Pages (from-to)1231-1241
Number of pages11
JournalNeuron
Volume20
Issue number6
DOIs
StatePublished - Jun 1998

Funding

We would like to thank Dr. Stephen Cannon and Vasanth Vedantham (Massachusetts General Hospital) for advice with and the use of their oocyte setup, Dr. Miguel Holmgren for initial help with HEK 293 cells, and Drs. Jeffrey Holt, and Robert Waterston for helpful discussions. This research was supported by the Howard Hughes Medical Institute, by a postdoctoral fellowship from the Ramón Areces foundation (to J. G.-A.), and by an National Institutes of Health Minority National Research Service Award Predoctoral Fellowship (to J. A. G.). D. P. C. is an Investigator and J. G.-A. is an Associate of the Howard Hughes Medical Institute.

ASJC Scopus subject areas

  • General Neuroscience

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