Linked Life Data

12388596

Source:http://linkedlifedata.com/resource/pubmed/id/12388596

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2002-10-21
pubmed:abstractText
The 43 kDa receptor-associated protein rapsyn is a myristoylated peripheral protein that plays a central role in nicotinic acetylcholine receptor (AChR) clustering at the neuromuscular junction. In a previous study, we demonstrated that rapsyn is specifically cotransported with AChR via post-Golgi vesicles targeted to the innervated surface of the Torpedo electrocyte (Marchand et al., 2000). In the present study, to further elucidate the mechanisms for sorting and assembly of postsynaptic proteins, we analyzed the dynamics of the intracellular trafficking of fluorescently labeled rapsyn in the transient-expressing COS-7 cell system. Our approach was based on fluorescence, time-lapse imaging, and immunoelectron microscopies, as well as biochemical analyses. We report that newly synthesized rapsyn associates with the trans-Golgi network compartment and traffics via vesiculotubular organelles toward the cell surface of COS-7 cells. The targeting of rapsyn organelles appeared to be mediated by a microtubule-dependent transport. Using cotransfection experiments of rapsyn and AChR, we observed that these two molecules codistribute within distal exocytic routes and at the plasma membrane. Triton X-100 extraction on ice and flotation gradient centrifugation demonstrated that rapsyn and AChR are recovered in low-density fractions enriched in two rafts markers: caveolin-1 and flotillin-1. We propose that sorting and targeting of these two companion molecules are mediated by association with cholesterol-sphingolipid-enriched raft microdomains. Collectively, these data highlight rapsyn as an itinerant vesicular protein that may play a dynamic role in the sorting and targeting of its companion receptor to the postsynaptic membrane. These data also raise the interesting hypothesis of the participation of the raft machinery in the targeting of signaling molecules to synaptic sites.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8891-901
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12388596-Animals, pubmed-meshheading:12388596-COS Cells, pubmed-meshheading:12388596-Caveolin 1, pubmed-meshheading:12388596-Caveolins, pubmed-meshheading:12388596-Cell Compartmentation, pubmed-meshheading:12388596-Cell Membrane, pubmed-meshheading:12388596-Exocytosis, pubmed-meshheading:12388596-Green Fluorescent Proteins, pubmed-meshheading:12388596-Luminescent Proteins, pubmed-meshheading:12388596-Membrane Microdomains, pubmed-meshheading:12388596-Membrane Proteins, pubmed-meshheading:12388596-Mice, pubmed-meshheading:12388596-Microscopy, Fluorescence, pubmed-meshheading:12388596-Microscopy, Immunoelectron, pubmed-meshheading:12388596-Microscopy, Video, pubmed-meshheading:12388596-Microtubules, pubmed-meshheading:12388596-Muscle Proteins, pubmed-meshheading:12388596-Organelles, pubmed-meshheading:12388596-Protein Transport, pubmed-meshheading:12388596-Receptors, Nicotinic, pubmed-meshheading:12388596-Recombinant Fusion Proteins, pubmed-meshheading:12388596-Subcellular Fractions, pubmed-meshheading:12388596-Transfection, pubmed-meshheading:12388596-trans-Golgi Network
pubmed:year
2002
pubmed:articleTitle
Rapsyn escorts the nicotinic acetylcholine receptor along the exocytic pathway via association with lipid rafts.
pubmed:affiliation
Biologie Cellulaire des Membranes, Département de Biologie Cellulaire, Institut Jacques Monod, Centre National de la Recherche Scientifique, Universités Paris 6 et 7, 75251, Paris Cedex 05, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't