Linked Life Data

17953664

Source:http://linkedlifedata.com/resource/pubmed/id/17953664

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-12-11
pubmed:abstractText
Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN) are neurotrophic factors for parasympathetic neurons including ciliary ganglion (CG) neurons. Recently, we have shown that survival and signaling mediated by GDNF in CG neurons essentially requires transforming growth factor beta (TGFbeta). We have provided evidence that TGFbeta regulates the availability of the glycosyl phosphatidylinositol (GPI)-anchored GDNF receptor alpha 1 (GFRalpha1) by promoting the recruitment of the receptor to the plasma membrane. We report now that in addition to GDNF, NRTN, but not persephin (PSPN) or artemin (ARTN), is able to promote survival of CG neurons. Interestingly, in contrast to GDNF, NRTN is not dependent on cooperation with TGFbeta, but efficiently promotes neuronal survival and intracellular signaling in the absence of TGFbeta. Additional treatment with TGFbeta does not further increase the NRTN response. Both NRTN and GDNF exclusively bind to and activate their cognate receptors, GFRalpha2 and GFRalpha1, respectively, as shown by the use of receptor-specific neutralizing antibodies. Immunocytochemical staining for the two receptors on the surface of CG neurons reveals that, in contrast to the effect on GFRalpha1, TGFbeta is not required for recruitment of GFRalpha2 to the plasma membrane. Moreover, binding of radioactively labeled GDNF but not NRTN is increased upon treatment of CG neurons with TGFbeta. Disruption of TGFbeta signaling does interfere with GDNF-, but not NRTN-mediated signaling and survival. We propose a model taking into account data from GFRalpha1 crystallization and ontogenetic development of the CG that may explain the differences in TGFbeta-dependence of GDNF and NRTN.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2491-504
pubmed:meshHeading
pubmed-meshheading:17953664-Animals, pubmed-meshheading:17953664-Cell Line, pubmed-meshheading:17953664-Cell Membrane, pubmed-meshheading:17953664-Cell Survival, pubmed-meshheading:17953664-Cells, Cultured, pubmed-meshheading:17953664-Chick Embryo, pubmed-meshheading:17953664-Ganglia, Parasympathetic, pubmed-meshheading:17953664-Glial Cell Line-Derived Neurotrophic Factor, pubmed-meshheading:17953664-Glial Cell Line-Derived Neurotrophic Factor Receptors, pubmed-meshheading:17953664-Glial Cell Line-Derived Neurotrophic Factors, pubmed-meshheading:17953664-Ligands, pubmed-meshheading:17953664-Mice, pubmed-meshheading:17953664-Models, Molecular, pubmed-meshheading:17953664-Neurons, pubmed-meshheading:17953664-Neurturin, pubmed-meshheading:17953664-Protein Binding, pubmed-meshheading:17953664-Protein Transport, pubmed-meshheading:17953664-Receptor Cross-Talk, pubmed-meshheading:17953664-Transforming Growth Factor beta
pubmed:year
2007
pubmed:articleTitle
Specificity in the crosstalk of TGFbeta/GDNF family members is determined by distinct GFR alpha receptors.
pubmed:affiliation
Department of Neuroanatomy, IZN, University of Heidelberg, Heidelberg, Germany. heike.peterziel@urz.uni-heidelberg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't