Linked Life Data

10995758

Source:http://linkedlifedata.com/resource/pubmed/id/10995758

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2001-1-18
pubmed:abstractText
The beta(1)-adrenergic receptor (beta(1)AR) is the most abundant subtype of beta-adrenergic receptor in the mammalian brain and is known to potently regulate synaptic plasticity. To search for potential neuronal beta(1)AR-interacting proteins, we screened a rat brain cDNA library using the beta(1)AR carboxyl terminus (beta(1)AR-CT) as bait in the yeast two-hybrid system. These screens identified PSD-95, a multiple PDZ domain-containing scaffolding protein, as a specific binding partner of the beta(1)AR-CT. This interaction was confirmed by in vitro fusion protein pull-down and blot overlay experiments, which demonstrated that the beta(1)AR-CT binds specifically to the third PDZ domain of PSD-95. Furthermore, the full-length beta(1)AR associates with PSD-95 in cells, as determined by co-immunoprecipitation experiments and immunofluorescence co-localization studies. The interaction between beta(1)AR and PSD-95 is mediated by the last few amino acids of the beta(1)AR, and mutation of the beta(1)AR carboxyl terminus eliminated the binding and disrupted the co-localization of the beta(1)AR and PSD-95 in cells. Agonist-induced internalization of the beta(1)AR in HEK-293 cells was markedly attenuated by PSD-95 co-expression, whereas co-expression of PSD-95 has no significant effect on either desensitization of the beta(1)AR or beta(1)AR-induced cAMP accumulation. Furthermore, PSD-95 facilitated the formation of a complex between the beta(1)AR and N-methyl-d-aspartate receptors, as assessed by co-immunoprecipitation. These data reveal that PSD-95 is a specific beta(1)AR binding partner that modulates beta(1)AR function and facilitates physical association of the beta(1)AR with synaptic proteins, such as the N-methyl-d-aspartate receptors, which are known to be regulated by beta(1)AR stimulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38659-66
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10995758-Animals, pubmed-meshheading:10995758-Brain, pubmed-meshheading:10995758-COS Cells, pubmed-meshheading:10995758-Cell Line, pubmed-meshheading:10995758-Cercopithecus aethiops, pubmed-meshheading:10995758-Cloning, Molecular, pubmed-meshheading:10995758-Gene Library, pubmed-meshheading:10995758-Humans, pubmed-meshheading:10995758-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:10995758-Membrane Proteins, pubmed-meshheading:10995758-Nerve Tissue Proteins, pubmed-meshheading:10995758-Peptide Fragments, pubmed-meshheading:10995758-Protein Binding, pubmed-meshheading:10995758-Protein Transport, pubmed-meshheading:10995758-Rats, pubmed-meshheading:10995758-Receptors, Adrenergic, beta-1, pubmed-meshheading:10995758-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:10995758-Recombinant Fusion Proteins, pubmed-meshheading:10995758-Saccharomyces cerevisiae, pubmed-meshheading:10995758-Transfection
pubmed:year
2000
pubmed:articleTitle
beta 1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of beta 1-adrenergic receptor interaction with N-methyl-D-aspartate receptors.
pubmed:affiliation
Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.