Mechanism underlying activity-dependent insertion of TrkB into the neuronal surface.
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.
Zhao
Ling
L
Department of Neurobiology, Key Laboratory of Medical Neurobiology, School of Medicine, Shandong University, Shandong, P.R. China.
Sheng
Ai-Li
AL
Huang
Shu-Hong
SH
Yin
Yu-Xia
YX
Chen
Bing
B
Li
Xue-Zhi
XZ
Zhang
Yun
Y
Chen
Zhe-Yu
ZY
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D007700:Kinetics; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D020813:Receptor, trkB; D051360:Cyclin-Dependent Kinase 5