PMID- 19351881 OWN - NLM STAT- MEDLINE DCOM- 20090629 LR - 20211020 IS - 0021-9258 (Print) IS - 1083-351X (Electronic) IS - 0021-9258 (Linking) VI - 284 IP - 22 DP - 2009 May 29 TI - Essential role of Hrs in endocytic recycling of full-length TrkB receptor but not its isoform TrkB.T1. PG - 15126-36 LID - 10.1074/jbc.M809763200 [doi] AB - Brain-derived neurotrophic factor (BDNF) signaling through its receptor, TrkB, modulates survival, differentiation, and synaptic activity of neurons. Both full-length TrkB (TrkB-FL) and its isoform T1 (TrkB.T1) receptors are expressed in neurons; however, whether they follow the same endocytic pathway after BDNF treatment is not known. In this study we report that TrkB-FL and TrkB.T1 receptors traverse divergent endocytic pathways after binding to BDNF. We provide evidence that in neurons TrkB.T1 receptors predominantly recycle back to the cell surface by a "default" mechanism. However, endocytosed TrkB-FL receptors recycle to a lesser extent in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner which relies on its tyrosine kinase activity. The distinct role of Hrs in promoting recycling of internalized TrkB-FL receptors is independent of its ubiquitin-interacting motif. Moreover, Hrs-sensitive TrkB-FL recycling plays a role in BDNF-induced prolonged mitogen-activated protein kinase (MAPK) activation. These observations provide evidence for differential postendocytic sorting of TrkB-FL and TrkB.T1 receptors to alternate intracellular pathways. FAU - Huang, Shu-Hong AU - Huang SH AD - Department of Neurobiology, Key Laboratory of Medical Neurobiology, School of Medicine, Jinan, Shandong 250012, China. FAU - Zhao, Ling AU - Zhao L FAU - Sun, Zong-Peng AU - Sun ZP FAU - Li, Xue-Zhi AU - Li XZ FAU - Geng, Zhao AU - Geng Z FAU - Zhang, Kai-Di AU - Zhang KD FAU - Chao, Moses V AU - Chao MV FAU - Chen, Zhe-Yu AU - Chen ZY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090407 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Endosomal Sorting Complexes Required for Transport) RN - 0 (Isoenzymes) RN - 0 (Ligands) RN - 0 (Phosphoproteins) RN - 0 (hepatocyte growth factor-regulated tyrosine kinase substrate) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Amino Acid Motifs MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Cell Line MH - *Endocytosis/drug effects MH - Endosomal Sorting Complexes Required for Transport MH - Enzyme Activation/drug effects MH - Humans MH - Isoenzymes/metabolism MH - Kinetics MH - Ligands MH - Mitogen-Activated Protein Kinases/metabolism MH - Models, Biological MH - Phosphoproteins/chemistry/*metabolism MH - Protein Processing, Post-Translational/drug effects MH - Protein Structure, Tertiary MH - Protein Transport/drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/chemistry/*metabolism MH - Signal Transduction/drug effects PMC - PMC2685694 EDAT- 2009/04/09 09:00 MHDA- 2009/06/30 09:00 PMCR- 2010/05/29 CRDT- 2009/04/09 09:00 PHST- 2009/04/09 09:00 [entrez] PHST- 2009/04/09 09:00 [pubmed] PHST- 2009/06/30 09:00 [medline] PHST- 2010/05/29 00:00 [pmc-release] AID - S0021-9258(19)82123-3 [pii] AID - 15126 [pii] AID - 10.1074/jbc.M809763200 [doi] PST - ppublish SO - J Biol Chem. 2009 May 29;284(22):15126-36. doi: 10.1074/jbc.M809763200. Epub 2009 Apr 7.