| Autor: |
Zhao L; Department of Neurobiology, Key Laboratory of Medical Neurobiology, School of Medicine, Shandong University, Shandong, P.R. China., Sheng AL, Huang SH, Yin YX, Chen B, Li XZ, Zhang Y, Chen ZY |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of cell science [J Cell Sci] 2009 Sep 01; Vol. 122 (Pt 17), pp. 3123-36. Date of Electronic Publication: 2009 Aug 11. |
| DOI: |
10.1242/jcs.047712 |
| Abstrakt: |
Activity-dependent insertion of tyrosine kinase receptor type 2 (TrkB receptor) into the plasma membrane can explain, in part, the preferential effect of brain-derived neurotrophic factor (BDNF) on active neurons; however, the detailed cellular and molecular mechanisms underlying this process are still unclear. In our study, we developed a fluorescence ratiometric assay for surface TrkB receptors to investigate the mechanisms of recruitment of TrkB to the plasma membrane following chemical long-term potentiation (cLTP) induction. We found that, in hippocampal neurons, the effect of cLTP-induced TrkB surface-recruitment occurred predominantly on neurites with rapid kinetics (t(1/2) of approximately 2.3 minutes) and was dependent on an intact cytoskeleton structure. Mutagenesis studies revealed that the juxtamembrane domain of TrkB is necessary and sufficient for its activity-dependent insertion into the plasma membrane. Moreover, we found that the phosphorylation of TrkB receptor at the Ser478 site by cyclin-dependent kinase 5 (Cdk5) is essential for cLTP-induced TrkB insertion into the neuronal surface. Finally, the degree of cLTP-induced TrkB surface-recruitment is higher in postsynaptic regions, which provides a potential mechanism for rapid enhancement of postsynaptic sensitivity to incoming BDNF signaling. Our studies provide new insights regarding neuronal activity-dependent surface delivery of TrkB receptor, which will advance our understanding of the modulatory role of TrkB in synaptic plasticity. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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