Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2005-8-1
pubmed:abstractText
Insulin increases glucose uptake into muscle via glucose transporter-4 (GLUT4) translocation to the cell membrane, but the regulated events in GLUT4 traffic are unknown. Here we focus on the role of class IA phosphatidylinositol (PI) 3-kinase and specific phosphoinositides in the steps of GLUT4 arrival and fusion with the membrane, using L6 muscle cells expressing GLUT4myc. To this end, we detected the availability of the myc epitope at the cell surface or intravesicular spaces and of the cytosol-facing C-terminal epitope, in cells and membrane lawns derived from them. We observed the following: (a) Wortmannin and LY294002 at concentrations that inhibit class IA PI 3-kinase reduced but did not abate the C terminus gain, yet the myc epitope was unavailable for detection unless lawns or cells were permeabilized, suggesting the presence of GLUT4myc in docked, unfused vesicles. Accordingly, GLUT4myc-containing vesicles were detected by immunoelectron microscopy of membranes from cells pretreated with wortmannin and insulin, but not insulin or wortmannin alone. (b) Insulin caused greater immunological availability of the C terminus than myc epitopes, suggesting that C terminus unmasking had occurred. Delivering phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3)) to intact cells significantly increased lawn-associated myc signal without C terminus gain. Conversely, phosphatidylinositol 3-phosphate (PI3P) increased the detection of C terminus epitope without any myc gain. We propose that insulin regulates GLUT4 membrane arrival, fusion, and C terminus unmasking, through distinct phosphoinositides. PI(3,4,5)P(3) causes arrival and fusion without unmasking, whereas PI3P causes arrival and unmasking without fusion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz..., http://linkedlifedata.com/resource/pubmed/chemical/Androstadienes, http://linkedlifedata.com/resource/pubmed/chemical/Chromones, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Glucose Transporter Type 4, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Monosaccharide Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Morpholines, http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Slc2a4 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28792-802
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15955810-Androstadienes, pubmed-meshheading:15955810-Animals, pubmed-meshheading:15955810-Cell Membrane, pubmed-meshheading:15955810-Chromones, pubmed-meshheading:15955810-DNA, Complementary, pubmed-meshheading:15955810-Enzyme Inhibitors, pubmed-meshheading:15955810-Genes, myc, pubmed-meshheading:15955810-Glucose Transporter Type 4, pubmed-meshheading:15955810-Insulin, pubmed-meshheading:15955810-Membrane Fusion, pubmed-meshheading:15955810-Monosaccharide Transport Proteins, pubmed-meshheading:15955810-Morpholines, pubmed-meshheading:15955810-Muscle, Skeletal, pubmed-meshheading:15955810-Muscle Proteins, pubmed-meshheading:15955810-Phosphatidylinositol 3-Kinases, pubmed-meshheading:15955810-Phosphatidylinositols, pubmed-meshheading:15955810-Rats, pubmed-meshheading:15955810-Recombinant Fusion Proteins
pubmed:year
2005
pubmed:articleTitle
Insulin regulates the membrane arrival, fusion, and C-terminal unmasking of glucose transporter-4 via distinct phosphoinositides.
pubmed:affiliation
Programme in Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't