PMID- 23977241 OWN - NLM STAT- MEDLINE DCOM- 20150122 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 8 DP - 2013 TI - SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF. PG - e72164 LID - 10.1371/journal.pone.0072164 [doi] LID - e72164 AB - Stimulation of neurons with brain-derived neurotrophic factor (BDNF) results in robust induction of SORLA, an intracellular sorting receptor of the VPS10P domain receptor gene family. However, the relevance of SORLA for BDNF-induced neuronal responses has not previously been investigated. We now demonstrate that SORLA is a sorting factor for the tropomyosin-related kinase receptor B (TrkB) that facilitates trafficking of this BDNF receptor between synaptic plasma membranes, post-synaptic densities, and cell soma, a step critical for neuronal signal transduction. Loss of SORLA expression results in impaired neuritic transport of TrkB and in blunted response to BDNF in primary neurons; and it aggravates neuromotoric deficits caused by low BDNF activity in a mouse model of Huntington's disease. Thus, our studies revealed a key role for SORLA in mediating BDNF trophic signaling by regulating the intracellular location of TrkB. FAU - Rohe, Michael AU - Rohe M AD - Molecular Cardiovascular Research, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany. michael.rohe@mdc-berlin.de FAU - Hartl, Daniela AU - Hartl D FAU - Fjorback, Anja Nawarecki AU - Fjorback AN FAU - Klose, Joachim AU - Klose J FAU - Willnow, Thomas E AU - Willnow TE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130819 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (LDL-Receptor Related Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Receptors, LDL) RN - 0 (SORL1 protein, human) RN - 0 (Sorl1 protein, mouse) RN - 7171WSG8A2 (BDNF protein, human) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (tropomyosin-related kinase-B, human) SB - IM MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology MH - Cell Line MH - Disease Models, Animal MH - Female MH - Gene Expression Regulation MH - Humans MH - Huntington Disease/*genetics/metabolism/physiopathology MH - LDL-Receptor Related Proteins/genetics/*metabolism MH - Male MH - Membrane Glycoproteins/genetics/*metabolism MH - Membrane Transport Proteins/genetics/*metabolism MH - Mice MH - Mice, Transgenic MH - Neurons/cytology/drug effects/*metabolism MH - Primary Cell Culture MH - Protein Transport MH - Protein-Tyrosine Kinases/genetics/*metabolism MH - Receptor, trkB MH - Receptors, LDL/genetics/*metabolism MH - Signal Transduction MH - Synapses/drug effects/genetics PMC - PMC3747043 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/08/27 06:00 MHDA- 2015/01/23 06:00 PMCR- 2013/08/19 CRDT- 2013/08/27 06:00 PHST- 2013/04/21 00:00 [received] PHST- 2013/07/07 00:00 [accepted] PHST- 2013/08/27 06:00 [entrez] PHST- 2013/08/27 06:00 [pubmed] PHST- 2015/01/23 06:00 [medline] PHST- 2013/08/19 00:00 [pmc-release] AID - PONE-D-13-16383 [pii] AID - 10.1371/journal.pone.0072164 [doi] PST - epublish SO - PLoS One. 2013 Aug 19;8(8):e72164. doi: 10.1371/journal.pone.0072164. eCollection 2013.