title: Distinct modes of regulated receptor insertion to the somatodendritic plasma membrane.
abstract: Many neural signaling receptors are regulated by endocytosis, but little is known about receptor insertion into the plasma membrane. Time-lapse imaging of the beta2 adrenergic receptor expressed in cultured rat hippocampal neurons, using pH-sensitive green fluorescent protein tagging and total internal reflection fluorescence microscopy, resolved distinct vesicular fusion events mediating receptor insertion into the somatodendritic plasma membrane. A 'transient' insertion mode resulted in rapid lateral dispersion of receptors immediately after insertion. A 'persistent' insertion mode resulted in the retention of inserted receptors in surface-accessible domains, which were relatively immobile for a prolonged 'wait' period before dispersing laterally. Distinct insertion modes were oppositely regulated by receptor activation and by mechanisms differing in their dependence on the signaling effector cyclic AMP-dependent protein kinase. These results reveal a new mechanism for homeostatic regulation of postsynaptic signaling and a 'kiss-and-wait' mode of regulated membrane protein insertion in neurons.
authors.affiliation: Department of Psychiatry, University of California San Francisco, 600 16th Street, San Francisco, California 94143, USA.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Yudowski
authors.forename: Manojkumar A
authors.initials: MA
authors.lastname: Puthenveedu
authors.forename: Mark
authors.initials: M
authors.lastname: von Zastrow
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003952:Diagnostic Imaging / Q000379:methods; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007211:Indoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D018715:Microscopy, Video / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: D000318:Adrenergic beta-Agonists; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; C485187:PHluorin; D011758:Pyrroles; D018343:Receptors, Adrenergic, beta-2; D049452:Green Fluorescent Proteins; C057416:KT 5720; D007545:Isoproterenol