The Journal of Neuroscience, June 13, 2007, ():
Coregulation of Natively Expressed Pertussis Toxin-Sensitive Muscarinic Receptors with G-Protein-Activated Potassium Channels
J. Neurosci. Clancy et al.
27: 6388
Supplemental Data
Files in this Data Supplement:
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Figure S1: Model for co-regulation of m2/m4 muscarinic receptor/Kir3.2 signaling complexes in NGF-differentiated PC12 cells. (A) During increased cholinergic activation, the m2/m4 muscarinic receptor/Kir3 channel complexes are endocytosed from the plasma membrane, accumulate within the cytoplasm, and subsequently traffic to the endoplasmic reticulum and Golgi apparatus (Liste et al., 2002; Bernard et al., 2003). We hypothesize that a small reserve of m2/m4 muscarinic receptor/Kir3.2c channel complexes remain on the cell membrane, to respond to atropine. Following endocytosis, fewer m2/m4 muscarinic receptor/Kir3.2c channel complexes enter the recycling pathway, whereas the number of complexes entering the late endosome or lysosomal pathway increases (‘endosome’); thus contributing to reduced plasma membrane expression. We speculate that the PTX-sensitive G proteins also move with the m2/m4 receptors and Kir3.2c channels, since the G protein heterotrimer binds directly to the channel and receptor (Clancy et al., 2005). (B) In the presence of muscarinic receptor antagonists, cholinergic stimulation is attenuated, which leads to a decrease in endocytosis of m2/m4 muscarinic receptor/Kir3.2c channel complexes. In addition, m2/m4 muscarinic receptor/Kir3.2c channel complexes could be re-targeted from the late endosome or lysosomal pathway to the cell membrane. Thus, prolonged stimulation of m2/m4 muscarinic receptors regulates Kir3 signaling.
