Linked Life Data

15117940

Source:http://linkedlifedata.com/resource/pubmed/id/15117940

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2004-7-12
pubmed:abstractText
Receptors as well as some G protein subunits internalize after agonist stimulation. It is not clear whether Galpha(q) or Gbetagamma undergo such regulated translocation. Recent studies demonstrate that m3 muscarinic receptor activation in SK-N-SH neuroblastoma cells causes recruitment of tubulin to the plasma membrane. This subsequently transactivates Galpha(q) and activates phospholipase Cbeta1. Interaction of tubulin-GDP with Gbetagamma at the offset of phospholipase Cbeta1 signaling appears involved in translocation of tubulin and Gbetagamma to vesicle-like structures in the cytosol (Popova, J. S., and Rasenick, M. M. (2003) J. Biol. Chem. 278, 34299-34308). The relationship of this internalization to the clathrin-mediated endocytosis of the activated m3 muscarinic receptors or Galpha(q) involvement in this process has not been clarified. To test this, SK-N-SH cells were treated with carbachol, and localization of Galpha(q), Gbetagamma, tubulin, clathrin, and m3 receptors were analyzed by both cellular imaging and biochemical techniques. Upon agonist stimulation both tubulin and clathrin translocated to the plasma membrane and co-localized with receptors, Galpha(q) and Gbetagamma. Fifteen minutes later receptors, Gbetagamma and tubulin, but not Galpha(q), internalized with the clathrin-coated vesicles. Coimmunoprecipitation of m3 receptors with Gbetagamma, tubulin, and clathrin from the cytosol of carbachol-treated cells was readily observed. These data suggested that Gbetagamma subunits might organize the formation of a multiprotein complex linking m3 receptors to tubulin since they interacted with both proteins. Such protein assemblies might explain the dynamin-dependent but beta-arrestin-independent endocytosis of m3 muscarinic receptors since tubulin interaction with dynamin might guide or insert the complex into clathrin-coated pits. This novel mechanism of internalization might prove important for other beta-arrestin-independent endocytic pathways. It also suggests cross-regulation between G protein-mediated signaling and the dynamics of the microtubule cytoskeleton.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30410-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15117940-Blotting, Western, pubmed-meshheading:15117940-Carbachol, pubmed-meshheading:15117940-Cell Line, pubmed-meshheading:15117940-Cell Line, Tumor, pubmed-meshheading:15117940-Cell Membrane, pubmed-meshheading:15117940-Clathrin, pubmed-meshheading:15117940-Cytoskeleton, pubmed-meshheading:15117940-Cytosol, pubmed-meshheading:15117940-DNA, Complementary, pubmed-meshheading:15117940-Dynamins, pubmed-meshheading:15117940-Endocytosis, pubmed-meshheading:15117940-GTP-Binding Protein beta Subunits, pubmed-meshheading:15117940-GTP-Binding Protein gamma Subunits, pubmed-meshheading:15117940-Genes, Dominant, pubmed-meshheading:15117940-Humans, pubmed-meshheading:15117940-Microscopy, Confocal, pubmed-meshheading:15117940-Microscopy, Fluorescence, pubmed-meshheading:15117940-Microtubules, pubmed-meshheading:15117940-Precipitin Tests, pubmed-meshheading:15117940-Protein Binding, pubmed-meshheading:15117940-Protein Transport, pubmed-meshheading:15117940-Receptor, Muscarinic M3, pubmed-meshheading:15117940-Signal Transduction, pubmed-meshheading:15117940-Time Factors, pubmed-meshheading:15117940-Transcriptional Activation, pubmed-meshheading:15117940-Tubulin, pubmed-meshheading:15117940-Type C Phospholipases
pubmed:year
2004
pubmed:articleTitle
Clathrin-mediated endocytosis of m3 muscarinic receptors. Roles for Gbetagamma and tubulin.
pubmed:affiliation
Department of Physiology, College of Medicine, University of Illinois, Chicago, Illinois 60612-7342, USA. jsp@uic.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.