PMID- 12202482 OWN - NLM STAT- MEDLINE DCOM- 20030206 LR - 20220310 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 277 IP - 45 DP - 2002 Nov 8 TI - Regulation of TRKB surface expression by brain-derived neurotrophic factor and truncated TRKB isoforms. PG - 43160-7 AB - 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. FAU - Haapasalo, Annakaisa AU - Haapasalo A AD - Department of Neurobiology, University of Kuopio, P. O. Box 1627, 70211 Kuopio, Finland. FAU - Sipola, Ilkka AU - Sipola I FAU - Larsson, Kim AU - Larsson K FAU - Akerman, Karl E O AU - Akerman KE FAU - Stoilov, Peter AU - Stoilov P FAU - Stamm, Stefan AU - Stamm S FAU - Wong, Garry AU - Wong G FAU - Castren, Eero AU - Castren E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20020828 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA Primers) RN - 0 (Protein Isoforms) RN - 0 (Recombinant Proteins) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Base Sequence MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cell Membrane/*physiology MH - DNA Primers MH - *Gene Expression Regulation/drug effects MH - Hippocampus/physiology MH - Kinetics MH - Mice MH - Mutagenesis, Site-Directed MH - Neuroblastoma MH - Neurons/drug effects/*physiology MH - Point Mutation MH - Protein Isoforms/genetics/pharmacology MH - Receptor, trkB/*genetics MH - Recombinant Proteins MH - Sequence Deletion MH - Transfection MH - Tumor Cells, Cultured EDAT- 2002/08/31 10:00 MHDA- 2003/02/07 04:00 CRDT- 2002/08/31 10:00 PHST- 2002/08/31 10:00 [pubmed] PHST- 2003/02/07 04:00 [medline] PHST- 2002/08/31 10:00 [entrez] AID - S0021-9258(19)71918-8 [pii] AID - 10.1074/jbc.M205202200 [doi] PST - ppublish SO - J Biol Chem. 2002 Nov 8;277(45):43160-7. doi: 10.1074/jbc.M205202200. Epub 2002 Aug 28.