Neurotrophin receptors TrkB.T1 and p75NTR cooperate in modulating both functional and structural plasticity in mature hippocampal neurons

  title={Neurotrophin receptors TrkB.T1 and p75NTR cooperate in modulating both functional and structural plasticity in mature hippocampal neurons},
  author={Kristin Michaelsen and Marta Zagrebelsky and J Berndt-Huch and Martin Polack and Arne Buschler and Michael Sendtner and Martin Korte},
  journal={European Journal of Neuroscience},
Tropomyosin‐related kinase (Trk) receptors modulate neuronal structure and function both during development and in the mature nervous system. Interestingly, TrkB and TrkC are expressed as full‐length and as truncated splice variants. The cellular function of the kinase‐lacking isoforms remains so far unclear. We investigated the role of the truncated receptor TrkB.T1 in the hippocampus of transgenic mice overexpressing this splice variant by analyzing both neuronal structure and function. We… 
Imbalance of neurotrophin receptor isoforms TrkB-FL/TrkB-T1 induces neuronal death in excitotoxicity
A significant modification of TrkB expression is demonstrated that is strongly associated with neurodegeneration in models of ischemia and in vitro excitotoxicity, and novel targets for the design of stroke therapies are revealed.
Expression of full-length and truncated trkB in human striatum and substantia nigra neurons: implications for Parkinson’s disease
Reports on the regional and neuronal distribution of and tr.t1 in the striatum and substantia nigra pars compacta of human autopsy tissues from control and PD cases believe changes in trkB isoform distribution and expression levels may be markers of pathology and affect the neuronal response to BDNF.
Truncated TrkB: beyond a dominant negative receptor.
  • B. Fenner
  • Biology
    Cytokine & growth factor reviews
  • 2012
Function and Mechanisms of Truncated BDNF Receptor TrkB.T1 in Neuropathic Pain
Together, these studies support a potential role for astrocytic TrkB.T1 in hyperpathic pain and suggest that targeted strategies directed at this receptor may have therapeutic potential.
Dynamic Nature of the p75 Neurotrophin Receptor in Response to Injury and Disease
Future studies hold the promise of revealing a wealth of information on the multifaceted actions of the p75NTR that will inform the design of new neurotrophin-based therapies.
Brain ischaemia induces shedding of a BDNF‐scavenger ectodomain from TrkB receptors by excitotoxicity activation of metalloproteinases and γ‐secretases
TrkB‐FL and TrkB‐T1 are identified as new substrates of regulated intramembrane proteolysis (RIP) and reveal new targets for the rational design of therapies to treat stroke and other pathologies with an excitotoxic component.
Increased hippocampal NgR1 signaling machinery in aged rats with deficits of spatial cognition
Myelin‐associated inhibitor/NgR1 signaling has important roles in modulation of synaptic plasticity, with demonstrated effects on cognitive function. We have previously demonstrated that NgR1 and its
Neurobiology of local and intercellular BDNF signaling
Recent findings on local actions of the BDNF family of ligands at the synapse are considered and converging lines of evidence which emerge from per se conflicting results are discussed.
Suppression of p75 Neurotrophin Receptor Surface Expression with Intrabodies Influences Bcl-xL mRNA Expression and Neurite Outgrowth in PC12 Cells
The ER retained intrabody construct, SH325-G7-KDEL, mediated a downregulation of p75NTR cell surface expression as shown by flow cytometry, and not only induces phenotypic knockdown of this p75nTR but also p 75NTR-associated cellular responses in PC12 cells.


Endogenous Truncated TrkB.T1 Receptor Regulates Neuronal Complexity and TrkB Kinase Receptor Function In Vivo
The results suggest that, at the physiological level, Tr.T1 receptors are important regulators of TrkB.FL signaling in vivo and selectively affects dendrite complexity of certain neuronal populations.
Developmental and mature expression of full‐length and truncated TrkB, receptors in the rat forebrain
The dendritic localization of trkB receptors supports the hypothesis that dendrites, as well as axons, are important sites for neurotrophin actions in the central nervous system.
Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor
It is shown that overexpression of Tr.T1 in hippocampal neurons induces the formation of dendritic filopodia, which are known precursors of synaptic spines, and proposes a novel signalling pathway initiated by neurotrophin-independent extracellular or intramembrane interaction of TrkB.FL.
Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells
The results show that TrkB-T1 has a direct signalling role in mediating inositol-1,4,5-trisphosphate-dependent calcium release; in addition, they identify a previously unknown mechanism of neurotrophin action in the brain.
The p75 Neurotrophin Receptor Negatively Modulates Dendrite Complexity and Spine Density in Hippocampal Neurons
It is shown in loss-of-function experiments that postnatal hippocampal pyramidal cells in two mutant lines of p75NTR have a higher spine density and greater dendritic complexity than wild-type (WT) mice, and a new case of functional antagonism between Trk and p 75NTR signaling is documents.
Regulation of TRKB Surface Expression by Brain-derived Neurotrophic Factor and Truncated TRKB Isoforms*
It is reported here that BDNF regulates the cell surface levels of transfected or endogenously expressed full-length TRKB, depending on the exposure time in neuroblastoma cells and primary hippocampal neurons, and suggests that regulation of TRKB surface expression levels by different factors is tightly controlled by complex mechanisms in active neurons.
Naturally Occurring Truncated trkB Receptors Have Dominant Inhibitory Effects on Brain-Derived Neurotrophic Factor Signaling
The data suggest that naturally occurring truncated trkB receptors function as inhibitory modulators of neurotrophin responsiveness and the homodimerization of gp145trkB appears to be an essential step in activation of the BDNF signaling cascade.
Selective binding and internalisation by truncated receptors restrict the availability of BDNF during development.
Results suggest that truncated trkB molecules form an efficient and selective barrier preventing the diffusion of brain-derived neurotrophic factor and eliminating it by internalisation.