Distinct modes of regulated receptor insertion to the somatodendritic plasma membrane

Nat Neurosci. 2006 May;9(5):622-7. doi: 10.1038/nn1679. Epub 2006 Apr 9.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Carbazoles / pharmacology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Diagnostic Imaging / methods
  • Drug Interactions
  • Embryo, Mammalian
  • Enzyme Inhibitors / pharmacology
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology
  • Indoles / pharmacology
  • Isoproterenol / pharmacology
  • Microscopy, Video / methods
  • Microtubule-Associated Proteins / metabolism
  • Neurons / drug effects
  • Neurons / physiology
  • Neurons / ultrastructure*
  • Pyrroles / pharmacology
  • Rats
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Time Factors
  • Transfection / methods


  • Adrenergic beta-Agonists
  • Carbazoles
  • Enzyme Inhibitors
  • Indoles
  • MAP2 protein, rat
  • Microtubule-Associated Proteins
  • PHluorin
  • Pyrroles
  • Receptors, Adrenergic, beta-2
  • Green Fluorescent Proteins
  • KT 5720
  • Isoproterenol