title: Where no synapses go: gatekeepers of circuit remodeling and synaptic strength.
abstract: Growth inhibitory molecules in the adult mammalian central nervous system (CNS) have been implicated in the blocking of axonal sprouting and regeneration following injury. Prominent CNS regeneration inhibitors include Nogo-A, oligodendrocyte myelin glycoprotein (OMgp), and chondroitin sulfate proteoglycans (CSPGs), and a key question concerns their physiological role in the naïve CNS. Emerging evidence suggests novel functions in dendrites and at synapses of glutamatergic neurons. CNS regeneration inhibitors target the neuronal actin cytoskeleton to regulate dendritic spine maturation, long-term synapse stability, and Hebbian forms of synaptic plasticity. This is accomplished in part by antagonizing plasticity-promoting signaling pathways activated by neurotrophic factors. Altered function of CNS regeneration inhibitors is associated with mental illness and loss of long-lasting memory, suggesting unexpected and novel physiological roles for these molecules in brain health.
authors: Department of Cell and Developmental Biology, University of Michigan School of Medicine, 3065 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
authors: Yevgeniya A
authors: YA
authors: Mironova
authors: Roman J
authors: RJ
authors: Giger
mesh_terms: D000647:Amnesia / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000254:growth & development / Q000502:physiology; D001930:Brain Injuries / Q000503:physiopathology / Q000628:therapy; D011508:Chondroitin Sulfate Proteoglycans / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D023882:Dominance, Ocular / Q000502:physiology; D058851:GPI-Linked Proteins / Q000502:physiology; D006025:Glycosaminoglycans / Q000502:physiology; D006801:Humans; D001523:Mental Disorders / Q000503:physiopathology; D051379:Mice; D008959:Models, Neurological; D009185:Myelin Proteins / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy; D013569:Synapses / Q000502:physiology*
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D058851:GPI-Linked Proteins; D006025:Glycosaminoglycans; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; C560528:OMG protein, human; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse
references: Eur J Neurosci. 2002 Oct;16(7):1313-24
references: 12405992
references: J Cell Biol. 2010 Jan 25;188(2):271-85
references: 20083601
references: Nat Rev Neurosci. 2006 Aug;7(8):617-27
references: 16858390
references: Science. 2011 Apr 22;332(6028):484-8
references: 21454754
references: J Neurochem. 2012 Jul;122(1):147-61
references: 22519304
references: Curr Opin Neurobiol. 2011 Feb;21(1):132-43
references: 20832286
references: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8517-22
references: 16709670
references: Neuron. 2001 Sep 27;31(6):1001-13
references: 11580899
references: Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20476-81
references: 19915139
references: J Biol Chem. 2012 Oct 26;287(44):37171-84
references: 22923615
references: J Neurosci. 2011 Apr 27;31(17):6481-92
references: 21525289
references: Neuron. 2004 Oct 28;44(3):439-51
references: 15504325
references: J Neurosci. 2010 Oct 6;30(40):13220-34
references: 20926648
references: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8412-7
references: 12060784
references: J Neurosci. 2008 Jan 30;28(5):1262-9
references: 18234903
references: Nature. 2012 May 27;486(7403):410-4
references: 22722203
references: Neuron. 2013 Mar 6;77(5):859-66
references: 23473316
references: Neuron. 2012 Feb 9;73(3):466-81
references: 22325200
references: Eur J Neurosci. 2008 Jan;27(1):1-11
references: 18093178
references: J Neurosci. 2003 Dec 17;23(37):11770-7
references: 14684879
references: Cold Spring Harb Perspect Biol. 2010 Jul;2(7):a001867
references: 20519341
references: Science. 2006 Sep 22;313(5794):1792-5
references: 16990550
references: Mol Cell Biol. 2002 Nov;22(21):7417-27
references: 12370289
references: J Cell Sci. 2013 Jan 1;126(Pt 1):209-20
references: 23132925
references: Mol Cell Neurosci. 2009 Dec;42(4):363-71
references: 19699797
references: Dev Neurosci. 2010;32(4):313-20
references: 20938157
references: Science. 2009 Sep 4;325(5945):1258-61
references: 19729657
references: J Neurosci. 2004 Nov 17;24(46):10511-20
references: 15548666
references: J Neurosci. 2010 May 12;30(19):6607-12
references: 20463223
references: Brain Res. 1997 Aug 1;764(1-2):1-8
references: 9295187
references: Nat Neurosci. 2004 Mar;7(3):269-77
references: 14966523
references: Cell Tissue Res. 2003 Mar;311(3):333-42
references: 12658441
references: Mol Brain. 2008 Oct 15;1:10
references: 18922173
references: Neuron. 2010 Jun 10;66(5):663-70
references: 20547125
references: Neurosci Lett. 2012 Feb 21;510(1):58-61
references: 22260793
references: Neuron. 2007 Jan 18;53(2):217-32
references: 17224404
references: J Neurosci. 2010 May 19;30(20):6825-37
references: 20484625
references: Nat Neurosci. 2009 Sep;12(9):1145-51
references: 19668200
references: Science. 2006 Sep 22;313(5794):1795-800
references: 16917027
references: Neuroscience. 2004;124(4):841-55
references: 15026125
references: J Neurosci. 2012 Dec 12;32(50):18009-17, 18017a
references: 23238717
references: Brain Res. 2009 Sep 8;1288:105-15
references: 19555673
references: Nat Rev Neurosci. 2009 Sep;10(9):647-58
references: 19693029
references: Science. 1998 Nov 6;282(5391):1117-21
references: 9804549
references: Nat Rev Neurosci. 2010 Nov;11(11):735-46
references: 20944663
references: J Neurosci. 2009 May 13;29(19):6348-52
references: 19439611
references: Ann N Y Acad Sci. 2010 Jun;1198 Suppl 1:E22-34
references: 20590535
references: Science. 2003 Nov 7;302(5647):1044-6
references: 14605369
references: Curr Opin Neurobiol. 2008 Feb;18(1):101-7
references: 18534841
references: J Neurosci. 2012 Jun 13;32(24):8127-37
references: 22699894
references: J Neurosci. 2005 Apr 6;25(14):3613-20
references: 15814792
references: J Neurosci. 2005 Jan 26;25(4):808-22
references: 15673660
references: Cell. 2008 Aug 8;134(3):508-20
references: 18692473
references: J Biol Chem. 2010 Feb 26;285(9):6425-33
references: 20018888
references: J Neurosci. 2002 Jul 1;22(13):5505-15
references: 12097502
references: FASEB J. 2011 Sep;25(9):3146-56
references: 21670066
references: Glycobiology. 2012 Jul;22(7):1007-16
references: 22496542
references: Exp Neurol. 2012 May;235(1):33-42
references: 21596039
references: Brain. 2010 Aug;133(Pt 8):2331-47
references: 20566484
references: J Neurotrauma. 2013 Mar 1;30(5):413-25
references: 23438307
references: J Cell Sci. 2004 Sep 1;117(Pt 19):4591-602
references: 15331667
references: Mol Cell Neurosci. 2002 Sep;21(1):158-72
references: 12359158
references: Science. 2002 Nov 8;298(5596):1248-51
references: 12424383
references: Neurobiol Dis. 2013 Jun;54:150-7
references: 23369871
references: J Neurosci. 2010 Sep 15;30(37):12432-45
references: 20844138
references: Nat Rev Neurosci. 2004 Feb;5(2):146-56
references: 14735117
references: J Neurosci. 2007 Jul 4;27(27):7117-24
references: 17611264
references: J Neurochem. 2011 Dec;119(6):1183-93
references: 21985178
references: Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2569-74
references: 21262805
references: Exp Neurol. 2012 May;235(1):26-32
references: 21946272
references: J Cell Sci. 2008 Sep 15;121(Pt 18):3083-91
references: 18768934
references: Neuron. 2004 Sep 30;44(1):59-73
references: 15450160
references: Neural Dev. 2009 May 23;4:18
references: 19463192
references: Science. 2011 Aug 5;333(6043):769-73
references: 21817055
references: Neuron. 2004 Nov 18;44(4):609-21
references: 15541310
references: Mol Cell Neurosci. 2005 Aug;29(4):545-58
references: 15936953
references: Nat Neurosci. 2012 Jan 15;15(3):414-22, S1-2
references: 22246436
references: J Cell Sci. 2006 Jul 1;119(Pt 13):2787-96
references: 16772333
references: Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):4768-73
references: 22411830
references: Mol Cell Biol. 2004 Oct;24(20):8872-83
references: 15456862
references: Nat Neurosci. 2012 Mar 11;15(5):703-12
references: 22406547
references: Neuron. 2002 Mar 28;34(1):27-38
references: 11931739
references: Genes Dev. 2012 Oct 1;26(19):2222-35
references: 23028146
references: J Neurosci. 2008 Mar 12;28(11):2753-65
references: 18337405
references: J Neurosci. 2011 Apr 27;31(17):6289-95
references: 21525268
references: J Neurosci. 2011 Nov 23;31(47):17091-102
references: 22114278
references: J Neurosci. 2008 Dec 3;28(49):13161-72
references: 19052207
references: J Biol Chem. 2012 Apr 20;287(17):13822-8
references: 22389491
references: Neuron. 2004 Dec 16;44(6):961-75
references: 15603739
references: Nature. 2009 Dec 24;462(7276):1065-9
references: 20010807
references: J Neurosci. 2011 Oct 5;31(40):14051-66
references: 21976490
references: J Biol Chem. 2011 Sep 9;286(36):31418-24
references: 21768085
references: J Neurosci. 2006 Feb 8;26(6):1813-22
references: 16467530
references: Annu Rev Cell Dev Biol. 2011;27:697-729
references: 21740233
references: Eur J Neurosci. 2011 Jun;33(12):2187-202
references: 21615557
references: Science. 2009 Oct 23;326(5952):592-6
references: 19833921
references: Nat Neurosci. 2012 Jan 29;15(3):389-98, S1-2
references: 22286174
references: Nat Neurosci. 2005 Apr;8(4):458-67
references: 15750591
references: Science. 2005 Sep 30;309(5744):2222-6
references: 16195464
references: Neurosci Res. 2011 May;70(1):24-9
references: 21352859
references: Neuron. 2005 Jan 20;45(2):279-91
references: 15664179
references: J Neurosci. 2006 Feb 1;26(5):1386-95
references: 16452662
references: Science. 2008 Nov 7;322(5903):967-70
references: 18988857
references: Neuron. 2006 Feb 16;49(4):517-31
references: 16476662
references: Nat Neurosci. 2009 Jul;12(7):897-904
references: 19483686
references: J Neurosci. 2011 Sep 21;31(38):13485-99
references: 21940441
references: Neuron. 2009 Nov 25;64(4):463-70
references: 19945389
references: J Biol Chem. 2008 Jun 13;283(24):16641-52
references: 18411262
references: Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1205-10
references: 15647357
references: J Neurosci. 2012 Jul 4;32(27):9429-37
references: 22764251