title: SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF.
abstract: 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.
authors: Molecular Cardiovascular Research, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany. michael.rohe@mdc-berlin.de
authors: Michael
authors: M
authors: Rohe
authors: Daniela
authors: D
authors: Hartl
authors: Anja Nawarecki
authors: AN
authors: Fjorback
authors: Joachim
authors: J
authors: Klose
authors: Thomas E
authors: TE
authors: Willnow
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020813:Receptor, trkB; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013569:Synapses / Q000187:drug effects / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D026502:LDL-Receptor Related Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D011973:Receptors, LDL; C102582:SORL1 protein, human; C491168:Sorl1 protein, mouse; C579455:BDNF protein, human; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human
references: Nat Neurosci. 2011 Jan;14(1):54-61
references: 21102451
references: J Biol Chem. 2007 Nov 9;282(45):32956-64
references: 17855360
references: Methods Mol Biol. 2009;519:171-96
references: 19381583
references: Cell. 2004 Jul 9;118(1):127-38
references: 15242649
references: Nat Rev Neurosci. 2008 Dec;9(12):899-909
references: 19002190
references: Curr Protoc Neurosci. 2008 Jan;Chapter 1:Unit 1.16
references: 18428670
references: J Neurosci. 2009 Dec 9;29(49):15472-8
references: 20007471
references: J Neurosci. 2012 Jan 25;32(4):1467-80
references: 22279231
references: Nature. 1997 Oct 23;389(6653):856-60
references: 9349818
references: Cancer Res. 1973 Nov;33(11):2643-52
references: 4748425
references: Curr Opin Neurobiol. 2002 Jun;12(3):268-74
references: 12049932
references: Nat Rev Neurosci. 2003 Apr;4(4):299-309
references: 12671646
references: Brain Res. 2000 Jun 2;866(1-2):257-61
references: 10825501
references: Nature. 1995 Mar 30;374(6521):450-3
references: 7700353
references: Hum Mol Genet. 1999 Mar;8(3):397-407
references: 9949199
references: Arch Neurol. 2004 Aug;61(8):1200-5
references: 15313836
references: J Neurosci. 2008 Nov 26;28(48):12877-86
references: 19036982
references: Proc Natl Acad Sci U S A. 1964 Jul;52:53-9
references: 14192657
references: Dev Cell. 2009 May;16(5):675-86
references: 19460344
references: Brain Res Mol Brain Res. 1997 Nov;51(1-2):220-8
references: 9427524
references: J Cell Biol. 1983 May;96(5):1374-88
references: 6404912
references: J Neurochem. 2005 Dec;95(5):1438-45
references: 16171514
references: Brain Res Bull. 2003 Sep 30;61(5):469-79
references: 13679245
references: Nat Rev Mol Cell Biol. 2009 Oct;10(10):682-96
references: 19773780
references: J Neurosci. 1997 Apr 1;17(7):2295-313
references: 9065491
references: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13461-6
references: 16174740
references: J Biol Chem. 2008 May 23;283(21):14826-34
references: 18362153
references: Eur J Neurosci. 2004 May;19(10):2799-807
references: 15147313
references: Methods Mol Biol. 2009;519:311-38
references: 19381592
references: Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1545-64
references: 16939974
references: Mol Cell Proteomics. 2009 Apr;8(4):720-34
references: 19043139
references: J Proteome Res. 2011 Apr 1;10(4):1459-67
references: 21265575
references: Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9909-14
references: 9275225