Tags

Type your tag names separated by a space and hit enter

An acidic amino acid in the N-methyl-D-aspartate receptor that is important for spermine stimulation.
Mol Pharmacol. 1995 Dec; 48(6):1087-98.MP

Abstract

The polyamine spermine has multiple effects on N-methyl-D-aspartate (NMDA) receptors, including "glycine-independent" stimulation, which is seen in the presence of saturating concentrations of glycine; "glycine-dependent" stimulation, which is due to an increase in the affinity of the receptor for glycine; and voltage-dependent block. These effects may involve three separate polyamine binding sites on the receptor. To identify amino acid residues that are important for spermine binding, we used site-directed mutagenesis to alter amino acids in and around a region of the NR1 subunit of the NMDA receptor that shows homology with PotD, a polyamine binding protein from Escherichia coli. Mutated subunits, expressed in heteromeric and homomeric NMDA receptors, were studied by voltage-clamp recording in Xenopus oocytes. Mutation of two acidic residues (E339-E342) to neutral amino acids reduced or abolished glycine-independent stimulation by spermine without affecting glycine-dependent stimulation or voltage-dependent block by spermine. Mutation of these residues also had modest effects on sensitivity to protons and to ifenprodil but did not alter sensitivity to glutamate and glycine or to voltage-dependent block by Mg2+. Residue E342 in NR1 appears to be critical for glycine-independent spermine stimulation. Mutations at equivalent positions in NR2A(E352Q) or NR2B(E353Q) had no effect on sensitivity to spermine, pH, or ifenprodil. Residue E342 in NR1 may form part of a discrete spermine binding site on the NMDA receptor or be involved in the mechanism of modulation by polyamines. This residue may also be involved in modulation by protons and ifenprodil.

Authors+Show Affiliations

Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8848009

Citation

Williams, K, et al. "An Acidic Amino Acid in the N-methyl-D-aspartate Receptor That Is Important for Spermine Stimulation." Molecular Pharmacology, vol. 48, no. 6, 1995, pp. 1087-98.
Williams K, Kashiwagi K, Fukuchi J, et al. An acidic amino acid in the N-methyl-D-aspartate receptor that is important for spermine stimulation. Mol Pharmacol. 1995;48(6):1087-98.
Williams, K., Kashiwagi, K., Fukuchi, J., & Igarashi, K. (1995). An acidic amino acid in the N-methyl-D-aspartate receptor that is important for spermine stimulation. Molecular Pharmacology, 48(6), 1087-98.
Williams K, et al. An Acidic Amino Acid in the N-methyl-D-aspartate Receptor That Is Important for Spermine Stimulation. Mol Pharmacol. 1995;48(6):1087-98. PubMed PMID: 8848009.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An acidic amino acid in the N-methyl-D-aspartate receptor that is important for spermine stimulation. AU - Williams,K, AU - Kashiwagi,K, AU - Fukuchi,J, AU - Igarashi,K, PY - 1995/12/1/pubmed PY - 1995/12/1/medline PY - 1995/12/1/entrez SP - 1087 EP - 98 JF - Molecular pharmacology JO - Mol Pharmacol VL - 48 IS - 6 N2 - The polyamine spermine has multiple effects on N-methyl-D-aspartate (NMDA) receptors, including "glycine-independent" stimulation, which is seen in the presence of saturating concentrations of glycine; "glycine-dependent" stimulation, which is due to an increase in the affinity of the receptor for glycine; and voltage-dependent block. These effects may involve three separate polyamine binding sites on the receptor. To identify amino acid residues that are important for spermine binding, we used site-directed mutagenesis to alter amino acids in and around a region of the NR1 subunit of the NMDA receptor that shows homology with PotD, a polyamine binding protein from Escherichia coli. Mutated subunits, expressed in heteromeric and homomeric NMDA receptors, were studied by voltage-clamp recording in Xenopus oocytes. Mutation of two acidic residues (E339-E342) to neutral amino acids reduced or abolished glycine-independent stimulation by spermine without affecting glycine-dependent stimulation or voltage-dependent block by spermine. Mutation of these residues also had modest effects on sensitivity to protons and to ifenprodil but did not alter sensitivity to glutamate and glycine or to voltage-dependent block by Mg2+. Residue E342 in NR1 appears to be critical for glycine-independent spermine stimulation. Mutations at equivalent positions in NR2A(E352Q) or NR2B(E353Q) had no effect on sensitivity to spermine, pH, or ifenprodil. Residue E342 in NR1 may form part of a discrete spermine binding site on the NMDA receptor or be involved in the mechanism of modulation by polyamines. This residue may also be involved in modulation by protons and ifenprodil. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/8848009/An_acidic_amino_acid_in_the_N_methyl_D_aspartate_receptor_that_is_important_for_spermine_stimulation_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8848009 DB - PRIME DP - Unbound Medicine ER -