+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

The A beta(1-42)M35C mutated amyloid peptide A beta(1-42)and the 25-35 fragment fail to mimic the subtype-specificity of actions on recombinant human nicotinic acetylcholine receptors (alpha 7, alpha 4 beta 2, alpha 3 beta 4)



The A beta(1-42)M35C mutated amyloid peptide A beta(1-42)and the 25-35 fragment fail to mimic the subtype-specificity of actions on recombinant human nicotinic acetylcholine receptors (alpha 7, alpha 4 beta 2, alpha 3 beta 4)



Neuroscience Letters 427(1): 28-33



Alzheimer's disease (AD) is a neurodegenerative condition involving accumulation of the P-amyloid peptide, A beta(1-42). Previously we have shown that amyloid peptides (A beta(1-42), A beta(1-40)) have different actions on the three major brain nicotinic acetylcholine receptor (nAChR) subtypes (alpha, alpha 4 beta 2 and alpha 3 beta 4). The methionine in position 35 of A beta (M35) has been shown to be important in the toxicity of A beta and the 25-35 fragment can mimic some of the actions of the A beta(1-42) peptide. However, the extent to which this mutant and the fragment mimic subtype selectivity is unknown. Two-electrode voltage-clamp electrophysiology has been used to study the actions on alpha 7, alpha 4 beta 2 and alpha 3 beta 4 recombinant nAChRs expressed in Xenopus laevis oocytes of full length A beta(1-42), and A beta peptide fragments, scrambled peptides, and the A beta(1-42) peptide containing mutations of the methionine in position 35. The A beta(25-35) fragment did not display subunit specificity. A beta(1-42) with an M35C mutation showed similar subtype-specificity to wild-type A beta(1-42). However, A beta(1-42) with an M35V substitution reduced the peak amplitude of ACh-induced currents recorded from alpha 4 beta 2 nAChRs, but did not affect those recorded from alpha 7 or alpha 3 beta 4. These results indicate that the amino acid in position 35 of A beta(1-42) is an important determinant of the subtype- specificity of this peptide on human recombinant alpha 7 alpha 4 beta 2 and alpha 3 beta 4 nAChRs and that the 25-35 fragment fails to mimic all of the actions of the full-length peptide.

(PDF emailed within 0-6 h: $19.90)

Accession: 021867725

Download citation: RISBibTeXText

PMID: 17945421

DOI: 10.1016/j.neulet.2007.08.041


Related references

Subtype-specific actions of beta-amyloid peptides on recombinant human neuronal nicotinic acetylcholine receptors (alpha 7, alpha 4 beta 2, alpha 3 beta 4) expressed in Xenopus laevis oocytes. British Journal of Pharmacology 146(7): 964-971, 2005

Pharmacological characterization of recombinant human neuronal nicotinic acetylcholine receptors h alpha 2 beta 2, h alpha 2 beta 4, h alpha 3 beta 2, h alpha 3 beta 4, h alpha 4 beta 2, h alpha 4 beta 4 and h alpha 7 expressed in Xenopus oocytes. Journal of Pharmacology and Experimental Therapeutics 280(1): 346-356, 1997

Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits. Journal of Molecular Neuroscience 7(3): 217-228, 1996

Structural differences determine the relative selectivity of nicotinic compounds for native alpha 4 beta 2*-, alpha 6 beta 2*-, alpha 3 beta 4*- and alpha 7-nicotine acetylcholine receptors. Neuropharmacology 58(7): 1054-1066, 2010

Characterization of recombinant human h-alpha-2-beta-2 and h-alpha-3-beta-2 neuronal nicotinic acetylcholine receptors. Society for Neuroscience Abstracts 23(1-2): 384, 1997

HEK293 cells stably expressing recombinant human neuronal nicotinic acetylcholine receptors alpha-3-beta-2 and alpha-4-beta-2 display differential sensitivity to external Ca-2+. Society for Neuroscience Abstracts 22(1-3): 1526, 1996

Polarized expression of integrin receptors (alpha 6 beta 4, alpha 2 beta 1, alpha 3 beta 1, and alpha v beta 5) and their relationship with the cytoskeleton and basement membrane matrix in cultured human keratinocytes. Journal of Cell Biology 112(4): 761-773, 1991

Cloning and functional expression of human neuronal nicotinic acetylcholine receptor subunit alpha-2, alpha-3, alpha-4, alpha-7, beta-2 and beta-4. Society for Neuroscience Abstracts 19(1-3): 69, 1993

Characterization of recombinant human neuronal nicotinic acetylcholine receptor subtypes alpha-4-beta-4 and alpha-2-beta-4 stably expressed in HEK293 cells. Society for Neuroscience Abstracts 21(1-3): 71, 1995

Characterization of human neuronal nicotinic acetylcholine receptors alpha-4-beta-2 and alpha-3-beta-2 stably expressed in HEK293 cells. Society for Neuroscience Abstracts 22(1-3): 1527, 1996

Rescue of amyloid-Beta-induced inhibition of nicotinic acetylcholine receptors by a peptide homologous to the nicotine binding domain of the alpha 7 subtype. Plos One 8(7): E67194, 2014

Regions of beta 2 and beta 4 responsible for differences between the steady state dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic receptors. Journal of General Physiology 105(6): 745-764, 1995

Heterologous expression of human {alpha}6{beta}4{beta}3{alpha}5 nicotinic acetylcholine receptors: binding properties consistent with their natural expression require quaternary subunit assembly including the {alpha}5 subunit. Journal of Pharmacology and Experimental Therapeutics 312(2): 619-626, 2004

Engineered topographic determinants with alpha beta, beta alpha beta, and beta alpha beta alpha topologies show high affinity binding to native protein antigen (lactate dehydrogenase-C4). Journal of Biological Chemistry 268(34): 25285-25295, 1993

A cyclic Arg-Gly-Asp containing pentapeptide, -SK and F-107260, binds integrin receptors alpha-IIb-beta-3, alpha-v-beta-3, and alpha-v-beta-5, but not alpha-5-beta-1, with high affinity. FASEB Journal 10(6): A1225, 1996