Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor.
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.
Hartmann
Matthias
M
Institute of Physiology and Pathophysiology, Johannes Gutenberg-University Mainz, Duesbergweg 6, 55128 Mainz, Germany.
Brigadski
Tanja
T
Erdmann
Kai S
KS
Holtmann
Bettina
B
Sendtner
Michael
M
Narz
Frank
F
Lessmann
Volkmar
V
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D003001:Cloning, Molecular; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism*; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D020813:Receptor, trkB / Q000378:metabolism / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D049452:Green Fluorescent Proteins; D020813:Receptor, trkB