Regulation of TRKB surface expression by brain-derived neurotrophic factor and truncated TRKB isoforms.
Brain-derived neurotrophic factor (BDNF) signaling through its receptor TRKB modulates survival, differentiation, and activity of neurons. BDNF activates TRKB on the cell surface, which leads to the initiation of intracellular signaling cascades and different biological responses in neurons. Neuronal activity has been shown to regulate TRKB levels on the plasma membrane of neurons, but little is known about other factors affecting TRKB surface expression levels. We report 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. BDNF rapidly increases TRKB surface expression levels in seconds, whereas treatment of cells with BDNF for a longer time (minutes to hours) leads to decreased TRKB surface levels. Coexpression of the full-length TRKB together with the truncated TRKB.T1 isoform results in decreased levels of full-length TRKB on the cell surface. This effect is specific to the T1 isoform, because coexpression of a kinase-dead TRKB mutant or another kinase domain-lacking TRKB form, truncated T-Shc, leads to increased TRKB surface levels. Our results suggest that regulation of TRKB surface expression levels by different factors is tightly controlled by complex mechanisms in active neurons.
Department of Neurobiology, University of Kuopio, P. O. Box 1627, 70211 Kuopio, Finland.
Annakaisa
A
Haapasalo
Ilkka
I
Sipola
Kim
K
Larsson
Karl E O
KE
Akerman
Peter
P
Stoilov
Stefan
S
Stamm
Garry
G
Wong
Eero
E
Castren
D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002462:Cell Membrane / Q000502:physiology*; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000502:physiology; D007700:Kinetics; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017354:Point Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000494:pharmacology; D020813:Receptor, trkB / Q000235:genetics*; D011994:Recombinant Proteins; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D020033:Protein Isoforms; D011994:Recombinant Proteins; D020813:Receptor, trkB