PMID- 29739881 OWN - NLM STAT- MEDLINE DCOM- 20191021 LR - 20191022 IS - 1937-9145 (Electronic) IS - 1945-0877 (Linking) VI - 11 IP - 529 DP - 2018 May 8 TI - The receptor tyrosine kinase TrkB signals without dimerization at the plasma membrane. LID - eaao4006 [pii] LID - 10.1126/scisignal.aao4006 [doi] AB - Tropomyosin-related tyrosine kinase B (TrkB) is the receptor for brain-derived neurotrophic factor (BDNF) and provides critical signaling that supports the development and function of the mammalian nervous system. Like other receptor tyrosine kinases (RTKs), TrkB is thought to signal as a dimer. Using cell imaging and biochemical assays, we found that TrkB acted as a monomeric receptor at the plasma membrane regardless of its binding to BDNF and initial activation. Dimerization occurred only after the internalization and accumulation of TrkB monomers within BDNF-containing endosomes. We further showed that dynamin-mediated endocytosis of TrkB-BDNF was required for the effective activation of the kinase AKT but not of the kinase ERK1/2. Thus, we report a previously uncharacterized mode of monomeric signaling for an RTK and a specific role for the endosome in TrkB homodimerization. CI - Copyright (c) 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. FAU - Zahavi, Eitan Erez AU - Zahavi EE AUID- ORCID: 0000-0002-9555-2654 AD - Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel. FAU - Steinberg, Noam AU - Steinberg N AD - Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel. FAU - Altman, Topaz AU - Altman T AUID- ORCID: 0000-0003-3075-894X AD - Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel. FAU - Chein, Michael AU - Chein M AD - Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel. AD - Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv 6997801, Israel. FAU - Joshi, Yuvraj AU - Joshi Y AD - Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel. FAU - Gradus-Pery, Tal AU - Gradus-Pery T AD - Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel. FAU - Perlson, Eran AU - Perlson E AUID- ORCID: 0000-0001-6047-9613 AD - Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel. eranpe@post.tau.ac.il. AD - Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv 6997801, Israel. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180508 PL - United States TA - Sci Signal JT - Science signaling JID - 101465400 RN - 0 (Bdnf protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - EC 2.7.10.1 (Ntrk2 protein, mouse) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.11.1 (Akt1 protein, mouse) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 3.6.5.5 (Dynamins) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cell Membrane/*metabolism MH - Dynamins/*metabolism MH - Endocytosis MH - Female MH - HEK293 Cells MH - Humans MH - Male MH - Membrane Glycoproteins/*chemistry/*metabolism MH - Mice MH - Mice, Inbred ICR MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Phosphorylation MH - *Protein Multimerization MH - Protein-Tyrosine Kinases/*chemistry/*metabolism MH - Proto-Oncogene Proteins c-akt/metabolism EDAT- 2018/05/10 06:00 MHDA- 2019/10/23 06:00 CRDT- 2018/05/10 06:00 PHST- 2018/05/10 06:00 [entrez] PHST- 2018/05/10 06:00 [pubmed] PHST- 2019/10/23 06:00 [medline] AID - 11/529/eaao4006 [pii] AID - 10.1126/scisignal.aao4006 [doi] PST - epublish SO - Sci Signal. 2018 May 8;11(529):eaao4006. doi: 10.1126/scisignal.aao4006.