Affordable Access

deepdyve-link
Publisher Website

Contribution of subunits to Caenorhabditis elegans levamisole-sensitive nicotinic receptor function.

Authors
  • Hernando, Guillermina
  • Bergé, Ignacio
  • Rayes, Diego
  • Bouzat, Cecilia
Type
Published Article
Journal
Molecular Pharmacology
Publisher
American Society for Pharmacology & Experimental Therapeutics
Publication Date
Sep 01, 2012
Volume
82
Issue
3
Pages
550–560
Identifiers
DOI: 10.1124/mol.112.079962
PMID: 22734069
Source
Medline
License
Unknown

Abstract

Caenorhabditis elegans muscle contains seven different nicotinic receptor (AChR) subunits, five of which have been shown to be components of adult levamisole-sensitive AChRs (L-AChRs). To elucidate the reason for such subunit diversity, we explore their functional roles in larva 1 (L1) muscle cells. Single-channel and macroscopic current recordings reveal that the α-type LEV-8 subunit is a component of native L1 L-AChRs but behaves as a nonessential subunit. It plays a key role in maintaining a low rate and extent of desensitization of L-AChRs. In the absence of the α-type ACR-8 subunit, L-AChR channel properties are not modified, thus indicating that ACR-8 is not a component of L1 L-AChRs. Together with our previous findings, this study reveals that L1 muscle cells express a main L-AChR type composed of five different subunits: UNC-38, UNC-63, UNC-29, LEV-1, and LEV-8. Analysis of a double lev-8; acr-8-null mutant, which shows an uncoordinated and levamisole-resistant phenotype, reveals that ACR-8 can replace LEV-8 in its absence, thus attributing a functional role to this subunit. Docking into homology modeled L-AChRs proposes that ACh forms the typical cation-π interaction, suggests why levamisole is less efficacious than ACh, and shows that ACR-8 can form activatable binding-sites, thus opening doors for elucidating subunit arrangement and anthelmintic selectivity.

Report this publication

Statistics

Seen <100 times