Brain-derived neurotrophic factor induces cell surface expression of short-form tenascin R complex in hippocampal postsynapses.
Brain-derived neurotrophic factor (BDNF) is involved in hippocampal functions such as learning and memory and it plays a crucial role in regulating synaptic plasticity. To investigate potential mechanisms by which BDNF participates in neuronal communication through postsynaptic membrane proteins, we generated monoclonal antibodies against the synaptoneurosomal particulate fraction of mouse brain. One of the monoclonal antibodies, termed mAb#27, was found to be useful for analyzing BDNF-induced externalization of synaptoneurosomal membrane proteins of the hippocampus. In dissociated neuronal cultures, BDNF stimulation increased mAb#27 immunoprecipitates of biotin-labeled proteins with apparent masses, 55kDa, 80kDa, 100kDa, 130kDa, 140kDa and 160kDa. The mAb#27 recognition molecules were located in specific hippocampal regions of the brain and at postsynaptic sites in cultured cells. Proteomic studies of the mAb#27 immunocomplex identified newly derived short forms of tenascin R (TNR) as the mAb#27 recognition molecule. Contactin 1, prostaglandin regulatory-like protein and GABA A receptor subunit beta3 were identified as TNR-associated proteins. These proteins were recruited to mAb#27 when BDNF was applied to cells in culture. Each molecules identified in the present study contributes to the postsynaptic plasticity or the active cycle of cellular vesicle membranes. The formation of the TNR complex may serve as an underlying basis for synaptic plasticity in the hippocampus. Our results demonstrate that BDNF plays a role in external molecular dynamics and is likely to regulate synaptic functions such as the enhancement of neuronal excitability through GABAergic neurons.
Maruyama
Etsuko
E
Cellular Biochemistry Laboratory, RIKEN, Saitama 351-0198, Japan. maruyama@proteo.gr.jp
Ogawa
Kenji
K
Endo
Shogo
S
Tsujimoto
Masafumi
M
Hashikawa
Tsutomu
T
Nabetani
Takuji
T
Tsugita
Akira
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D019208:Brain-Derived Neurotrophic Factor; D046912:Multiprotein Complexes; D020033:Protein Isoforms; D021122:Protein Subunits; D011963:Receptors, GABA-A; D019063:Tenascin; C074638:tenascin R