scholarly journals Regulation of TrkB receptor tyrosine kinase and its internalization by neuronal activity and Ca2+ influx

2003 ◽  
Vol 163 (2) ◽  
pp. 385-395 ◽  
Author(s):  
Jing Du ◽  
Linyin Feng ◽  
Eugene Zaitsev ◽  
Hyun-Soo Je ◽  
Xu-wen Liu ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Neuronal Activity ◽  
Cell Biology ◽  
Hippocampal Neurons ◽  
Electric Stimulation ◽  
Kinase Activity ◽  
Critical Role ◽  
Tyrosine Kinase Activity ◽  
Internalization Process ◽  
Activity Dependent

Internalization of the neurotrophin–Trk receptor complex is critical for many aspects of neurotrophin functions. The mechanisms governing the internalization process are unknown. Here, we report that neuronal activity facilitates the internalization of the receptor for brain-derived neurotrophic factor, TrkB, by potentiating its tyrosine kinase activity. Using three independent approaches, we show that electric stimulation of hippocampal neurons markedly enhances TrkB internalization. Electric stimulation also potentiates TrkB tyrosine kinase activity. The activity-dependent enhancement of TrkB internalization and its tyrosine kinase requires Ca2+ influx through N-methyl-d-aspartate receptors and Ca2+ channels. Inhibition of internalization had no effect on TrkB kinase, but inhibition of TrkB kinase prevents the modulation of TrkB internalization, suggesting a critical role of the tyrosine kinase in the activity-dependent receptor endocytosis. These results demonstrate an activity- and Ca2+-dependent modulation of TrkB tyrosine kinase and its internalization, and they provide new insights into the cell biology of tyrosine kinase receptors.

Modulation of Excitability in Aplysia Tail Sensory Neurons by Tyrosine Kinases

2001 ◽  
Vol 85 (6) ◽  
pp. 2398-2411 ◽  
Author(s):  
Angela L. Purcell ◽  
Thomas J. Carew
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Sensory Neurons ◽  
Tyrosine Kinases ◽  
Kinase Activity ◽  
Kinase Inhibitors ◽  
Direct Injection ◽  
Tyrosine Phosphatase ◽  
Tyrosine Kinase Activity ◽  
Activity Dependent

Tyrosine kinases have recently been shown to modulate synaptic plasticity and ion channel function. We show here that tyrosine kinases can also modulate both the baseline excitability state of Aplysia tail sensory neurons (SNs) as well as the excitability induced by the neuromodulator serotonin (5HT). First, we examined the effects of increasing and decreasing tyrosine kinase activity in the SNs. We found that tyrosine kinase inhibitors decrease baseline SN excitability in addition to attenuating the increase in excitability induced by 5HT. Conversely, functionally increasing cellular tyrosine kinase activity in the SNs by either inhibiting opposing tyrosine phosphatase activity or by direct injection of an active tyrosine kinase (Src) induces increases in SN excitability in the absence of 5HT. Second, we examined the interaction between protein kinase A (PKA), which is known to mediate 5HT-induced excitability changes in the SNs, and tyrosine kinases, in the enhancement of SN excitability. We found that the tyrosine kinases function downstream of PKA activation since tyrosine kinase inhibitors reduce excitability induced by activators of PKA. Finally, we examined the role of tyrosine kinases in other forms of 5HT-induced plasticity in the SNs. We found that while tyrosine kinase inhibitors attenuate excitability produced by 5HT, they have no effect on short-term facilitation (STF) of the SN-motor neuron (MN) synapse induced by 5HT. Thus tyrosine kinases modulate different forms of SN plasticity independently. Such differential modulation would have important consequences for activity-dependent plasticity in a variety of neural circuits.

scholarly journals Activity- and Ca2+-Dependent Modulation of Surface Expression of Brain-Derived Neurotrophic Factor Receptors in Hippocampal Neurons

2000 ◽  
Vol 150 (6) ◽  
pp. 1423-1434 ◽  
Author(s):  
Jing Du ◽  
Linyin Feng ◽  
Feng Yang ◽  
Bai Lu
Keyword(s):  
Neuronal Activity ◽  
Neurotrophic Factor ◽  
High Frequency ◽  
Hippocampal Neurons ◽  
Electric Stimulation ◽  
Low Frequency ◽  
Brain Derived Neurotrophic Factor ◽  
Dependent Manner ◽  
Tetanic Stimulation ◽  
Activity Dependent

Brain-derived neurotrophic factor (BDNF) has been shown to regulate neuronal survival and synaptic plasticity in the central nervous system (CNS) in an activity-dependent manner, but the underlying mechanisms remain unclear. Here we report that the number of BDNF receptor TrkB on the surface of hippocampal neurons can be enhanced by high frequency neuronal activity and synaptic transmission, and this effect is mediated by Ca2+ influx. Using membrane protein biotinylation as well as receptor binding assays, we show that field electric stimulation increased the number of TrkB on the surface of cultured hippocampal neurons. Immunofluorescence staining suggests that the electric stimulation facilitated the movement of TrkB from intracellular pool to the cell surface, particularly on neuronal processes. The number of surface TrkB was regulated only by high frequency tetanic stimulation, but not by low frequency stimulation. The activity dependent modulation appears to require Ca2+ influx, since treatment of the neurons with blockers of voltage-gated Ca2+ channels or NMDA receptors, or removal of extracellular Ca2+, severely attenuated the effect of electric stimulation. Moreover, inhibition of Ca2+/calmodulin-dependent kinase II (CaMKII) significantly reduced the effectiveness of the tetanic stimulation. These findings may help us to understand the role of neuronal activity in neurotrophin function and the mechanism for receptor tyrosine kinase signaling.

scholarly journals Neuronal Activity-Dependent Accumulation of Arc in Astrocytes

2020 ◽  
Author(s):  
Yuheng Jiang ◽  
Antonius M.J. VanDongen
Keyword(s):  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Early Gene ◽  
Dependent Manner ◽  
Pharmacological Agents ◽  
Network Activation ◽  
Term Potentiation ◽  
Activity Dependent

AbstractThe immediate-early gene Arc is a master regulator of synaptic plasticity and plays a critical role in memory consolidation. However, there has not been a comprehensive analysis of the itinerary of Arc protein, linking its function at different subcellular locations with corresponding time points after neuronal network activation. When cultured hippocampal neurons are treated with a combination of pharmacological agents to induce long term potentiation, they express high levels of Arc, allowing to study its spatiotemporal distribution. Our experiments show that neuronal activity-induced Arc expression was not restricted to neurons, but that its spatiotemporal dynamics involved a shift to astrocytes at a later timepoint. Specifically, astrocytic Arc is not due to endogenous transcription, but is dependent on the production of neuronal Arc and accumulates potentially via the recently reported intercellular transfer mechanism through Arc capsids. In conclusion, we found that Arc accumulates within astrocytes in a neuronal activity-dependent manner, which is independent of endogenous astrocytic Arc transcription, therefore highlighting the need to study the purpose of this pool of Arc, especially in learning and memory.

scholarly journals Acidic and basic fibroblast growth factors stimulate tyrosine kinase activity in vivo.

1988 ◽  
Vol 263 (2) ◽  
pp. 988-993 ◽  
Author(s):  
S R Coughlin ◽  
P J Barr ◽  
L S Cousens ◽  
L J Fretto ◽  
L T Williams
Keyword(s):  
Growth Factors ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Fibroblast Growth Factors ◽  
Fibroblast Growth ◽  
Tyrosine Kinase Activity
Sign in / Sign up

Export Citation Format

Share Document