The Mammalian Degenerin MDEG, an Amiloride-sensitive Cation Channel Activated by Mutations Causing Neurodegeneration in Caenorhabditis elegans(*)
- From the Institut de Pharmacologie Moléculaire et Cellulaire, UPR411 CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France
- § To whom correspondence should be addressed. Tel.: 33-93-95-77- 00 or 02; Fax: 33-93-95-77-04. douy{at}unice.fr.
Abstract
Mutations of the degenerins (deg-1, mec-4, mec-10) are the major known causes of hereditary neurodegeneration in the nematode
Caenorhabditis elegans. We cloned a neuronal degenerin (MDEG) from human and rat brain. MDEG is an amiloride-sensitive cation channel permeable
for Na
, K
, and Li
. This channel is activated by the same mutations which cause neurodegeneration in C. elegans. Like the hyperactive C. elegans degenerin mutants, constitutively active mutants of MDEG cause cell death, suggesting that gain of function of this novel
neuronal ion channel might be involved in human forms of neurodegeneration.
Footnotes
-
↵* This work was supported by CNRS and the Association Française contre les Myopathies (AFM). Bristol-Myers Squibb Co. supplied an “Unrestricted Award.” The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- PCR
-
polymerase chain reaction
- αNaCh
-
βNaCh,
NaCh, 
NaCh, amiloride-sensitive Na
channel α, β, 
, and 
subunits, respectively.
-
- Received February 5, 1996.
- Revision received March 10, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
