beta 1-Adrenergic Receptor Association with the Synaptic Scaffolding Protein Membrane-associated Guanylate Kinase Inverted-2 (MAGI-2). DIFFERENTIAL REGULATION OF RECEPTOR INTERNALIZATION BY MAGI-2 AND PSD-95 Export

@article{citeulike:3070841, abstract = {The [beta]1-adrenergic receptor ([beta]1AR) is known to be localized to synapses and to modulate synaptic plasticity in many brain regions, but the molecular mechanisms determining [beta]1AR subcellular localization are not fully understood. Using overlay and pull-down techniques, we found that the [beta]1AR carboxyl terminus associates with MAGI-2 (membrane-associated guanylate kinase inverted-2), a protein also known as S-SCAM (synaptic scaffolding molecule). MAGI-2 is a multidomain scaffolding protein that contains nine potential protein-protein interaction modules, including 6 PDZ domains, 2 WW domains, and a guanylate kinase-like domain. The [beta]1AR carboxyl terminus binds with high affinity to the first PDZ domain of MAGI-2, with the last few amino acids of the [beta]1AR carboxyl terminus being the key determinants of the interaction. In cells, the association of full-length [beta]1AR with MAGI-2 occurs constitutively and is enhanced by agonist stimulation of the receptor, as assessed by both co-immunoprecipitation experiments and immunofluorescence co-localization studies. Agonist-induced internalization of the [beta]1AR is markedly increased by co-expression with MAGI-2. Strikingly, this result is the opposite of the effect of co-expression with PSD-95, a previously reported binding partner of the [beta]1AR. Further cellular experiments revealed that MAGI-2 has no effect on [beta]1AR oligomerization but does promote association of [beta]1AR with the cytoplasmic signaling protein [beta]-catenin, a known MAGI-2 binding partner. These data reveal that MAGI-2 is a specific [beta]1AR binding partner that modulates [beta]1AR function and facilitates the physical association of the [beta]1AR with intracellular proteins involved in signal transduction and synaptic regulation. 10.1074/jbc.M107480200}, author = {Xu, Jianguo and Paquet, Maryse and Lau, Anthony G. and Wood, Jonathan D. and Ross, Christopher A. and Hall, Randy A.}, citeulike-article-id = {3070841}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M107480200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/276/44/41310}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/11526121}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=11526121}, day = {26}, doi = {10.1074/jbc.M107480200}, journal = {J. Biol. Chem.}, keywords = {bar, pdz, recycling}, month = {October}, number = {44}, pages = {41310--41317}, posted-at = {2008-08-01 10:55:32}, priority = {2}, title = {beta 1-Adrenergic Receptor Association with the Synaptic Scaffolding Protein Membrane-associated Guanylate Kinase Inverted-2 (MAGI-2). DIFFERENTIAL REGULATION OF RECEPTOR INTERNALIZATION BY MAGI-2 AND PSD-95}, url = {http://dx.doi.org/10.1074/jbc.M107480200}, volume = {276}, year = {2001} }

TY - JOUR ID - citeulike:3070841 L3 - citeulike-article-id:3070841 N2 - The [beta]1-adrenergic receptor ([beta]1AR) is known to be localized to synapses and to modulate synaptic plasticity in many brain regions, but the molecular mechanisms determining [beta]1AR subcellular localization are not fully understood. Using overlay and pull-down techniques, we found that the [beta]1AR carboxyl terminus associates with MAGI-2 (membrane-associated guanylate kinase inverted-2), a protein also known as S-SCAM (synaptic scaffolding molecule). MAGI-2 is a multidomain scaffolding protein that contains nine potential protein-protein interaction modules, including 6 PDZ domains, 2 WW domains, and a guanylate kinase-like domain. The [beta]1AR carboxyl terminus binds with high affinity to the first PDZ domain of MAGI-2, with the last few amino acids of the [beta]1AR carboxyl terminus being the key determinants of the interaction. In cells, the association of full-length [beta]1AR with MAGI-2 occurs constitutively and is enhanced by agonist stimulation of the receptor, as assessed by both co-immunoprecipitation experiments and immunofluorescence co-localization studies. Agonist-induced internalization of the [beta]1AR is markedly increased by co-expression with MAGI-2. Strikingly, this result is the opposite of the effect of co-expression with PSD-95, a previously reported binding partner of the [beta]1AR. Further cellular experiments revealed that MAGI-2 has no effect on [beta]1AR oligomerization but does promote association of [beta]1AR with the cytoplasmic signaling protein [beta]-catenin, a known MAGI-2 binding partner. These data reveal that MAGI-2 is a specific [beta]1AR binding partner that modulates [beta]1AR function and facilitates the physical association of the [beta]1AR with intracellular proteins involved in signal transduction and synaptic regulation. 10.1074/jbc.M107480200 IS - 44 JF - J. Biol. Chem. EP - 41317 TI - beta 1-Adrenergic Receptor Association with the Synaptic Scaffolding Protein Membrane-associated Guanylate Kinase Inverted-2 (MAGI-2). DIFFERENTIAL REGULATION OF RECEPTOR INTERNALIZATION BY MAGI-2 AND PSD-95 VL - 276 SP - 41310 KW - bar KW - pdz KW - recycling AU - Xu, Jianguo AU - Paquet, Maryse AU - Lau, Anthony AU - Wood, Jonathan AU - Ross, Christopher AU - Hall, Randy PY - 2001/10/26/ UR - http://dx.doi.org/10.1074/jbc.M107480200 ER -