Linked Life Data

12615964

Source:http://linkedlifedata.com/resource/pubmed/id/12615964

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 7
pubmed:dateCreated
2003-3-4
pubmed:abstractText
Exocytotic incorporation of plasmalemmal precursor vesicles (PPVs) into the cell surface is necessary for neurite extension and is known to occur mainly at the growth cone. This report examines whether this is a regulated event controlled by growth factors. The Golgi complex and nascent PPVs of hippocampal neurons in culture were pulse-labeled with fluorescent ceramide. We studied the dynamics of labeled PPVs upon arrival at the axonal growth cone. In controls and cultures stimulated with brain-derived neurotrophic factor (BDNF), PPV clusters persisted in growth cones with a half-life (t(1/2)) of >14 minutes. Upon challenge with IGF-1, however, fluorescent elements cleared from the growth cones with a t(1/2) of only 6 minutes. Plasmalemmal expansion was measured directly as externalization of membrane glycoconjugates in resealed growth cone particles (GCPs) isolated from fetal forebrain. These assays demonstrated that membrane expansion could be stimulated by IGF-1 in a dose-dependent manner but not by BDNF, even though intact, functional BDNF receptor was present on GCPs. Because both BDNF and IGF-1 are known to enhance neurite growth, but BDNF did not stimulate membrane expansion at the growth cone, we studied the effect of BDNF on the IGF-1 receptor. BDNF was found to cause the translocation of the growth-cone-specific IGF-1 receptor subunit beta(gc) to the distal axon, in a KIF2-dependent manner. We conclude that IGF-1 stimulates axonal assembly at the growth cone, and that this occurs via regulated exocytosis of PPVs. This mechanism is affected by BDNF only indirectly, by regulation of the beta(gc) level at the growth cone.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1209-17
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12615964-Animals, pubmed-meshheading:12615964-Brain, pubmed-meshheading:12615964-Brain-Derived Neurotrophic Factor, pubmed-meshheading:12615964-Cell Membrane, pubmed-meshheading:12615964-Cells, Cultured, pubmed-meshheading:12615964-Ceramides, pubmed-meshheading:12615964-Dose-Response Relationship, Drug, pubmed-meshheading:12615964-Exocytosis, pubmed-meshheading:12615964-Fetus, pubmed-meshheading:12615964-Fluorescent Dyes, pubmed-meshheading:12615964-Growth Cones, pubmed-meshheading:12615964-Growth Substances, pubmed-meshheading:12615964-Hippocampus, pubmed-meshheading:12615964-Insulin-Like Growth Factor I, pubmed-meshheading:12615964-Kinesin, pubmed-meshheading:12615964-Protein Subunits, pubmed-meshheading:12615964-Protein Transport, pubmed-meshheading:12615964-Rats, pubmed-meshheading:12615964-Receptor, IGF Type 1, pubmed-meshheading:12615964-Receptor, trkB, pubmed-meshheading:12615964-Transport Vesicles
pubmed:year
2003
pubmed:articleTitle
Regulation of membrane expansion at the nerve growth cone.
pubmed:affiliation
Department of Cellular and Structural Biology, University of Colorado, School of Medicine and Cancer Center, Denver, CO 80262, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't