Open AccessTruncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor
Author(s) -
Matthias Hartmann,
Tanja Brigadski,
Kai S. Erdmann,
Bettina Holtmann,
Michael Sendtner,
Frank Narz,
Volkmar Leßmann
Publication year - 2004
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.01511
Subject(s) - tropomyosin receptor kinase b , low affinity nerve growth factor receptor , biology , neurotrophin , tropomyosin receptor kinase a , microbiology and biotechnology , trk receptor , tropomyosin receptor kinase c , receptor tyrosine kinase , filopodia , tyrosine kinase , dendritic spine , neurotrophic factors , receptor , neuroscience , signal transduction , hippocampal formation , platelet derived growth factor receptor , biochemistry , growth factor , actin
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.