6533b7d2fe1ef96bd125f60f
RESEARCH PRODUCT
Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor.
Michael SendtnerFrank NarzKai S. ErdmannTanja BrigadskiBettina HoltmannVolkmar LeßmannMatthias HartmannMatthias Hartmannsubject
Time FactorsGreen Fluorescent ProteinsReceptors Nerve Growth FactorTropomyosin receptor kinase ATransfectionTropomyosin receptor kinase CHippocampusModels BiologicalPC12 CellsReceptor Nerve Growth FactorReceptor tyrosine kinaseLow-affinity nerve growth factor receptorAnimalsReceptor trkBNerve Growth FactorsPseudopodiaCloning MolecularNeuronsbiologyDose-Response Relationship Drugmusculoskeletal neural and ocular physiologyCell DifferentiationCell BiologyDendritesImmunohistochemistryDendritic filopodiaCell biologyProtein Structure TertiaryRatsnervous systemMicroscopy FluorescenceTrk receptorembryonic structuresNeurotrophin bindingCOS Cellsbiology.proteinsense organsNeurotrophinProtein BindingSignal Transductiondescription
The Trk family of receptor tyrosine kinases and the p75 receptor (p75NTR) mediate the effects of neurotrophins on neuronal survival, differentiation and synaptic plasticity. The neurotrophin BDNF and its cognate receptor tyrosine kinase, TrkB.FL, are highly expressed in neurons of the central nervous system. At later stages in postnatal development the truncated TrkB splice variants (TrkB.T1, TrkB.T2) become abundant. However, the signalling and function of these truncated receptors remained largely elusive.We show that overexpression of TrkB.T1 in hippocampal neurons induces the formation of dendritic filopodia, which are known precursors of synaptic spines. The induction of filopodia by TrkB.T1 occurs independently of neurotrophin binding and of kinase activity of endogenous TrkB.FL. Coexpression of a p75NTR lacking an intracellular domain inhibits the TrkB.T1-induced effect in a dominant negative manner. Steric hindrance of extracellular p75NTR interactions with a specific antibody, or absence of p75NTR with an intact extracellular domain also inhibit this TrkB.T1-induced effect.We thus propose a novel signalling pathway initiated by neurotrophin-independent extracellular or intramembrane interaction of TrkB.T1 with the p75NTR receptor, which modulates dendritic growth via p75NTR signalling cascades.
year | journal | country | edition | language |
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2004-10-28 | Journal of cell science |