title: CYY-1/cyclin Y and CDK-5 differentially regulate synapse elimination and formation for rewiring neural circuits.
abstract: The assembly and maturation of neural circuits require a delicate balance between synapse formation and elimination. The cellular and molecular mechanisms that coordinate synaptogenesis and synapse elimination are poorly understood. In C. elegans, DD motoneurons respecify their synaptic connectivity during development by completely eliminating existing synapses and forming new synapses without changing cell morphology. Using loss- and gain-of-function genetic approaches, we demonstrate that CYY-1, a cyclin box-containing protein, drives synapse removal in this process. In addition, cyclin-dependent kinase-5 (CDK-5) facilitates new synapse formation by regulating the transport of synaptic vesicles to the sites of synaptogenesis. Furthermore, we show that coordinated activation of UNC-104/Kinesin3 and Dynein is required for patterning newly formed synapses. During the remodeling process, presynaptic components from eliminated synapses are recycled to new synapses, suggesting that signaling mechanisms and molecular motors link the deconstruction of existing synapses and the assembly of new synapses during structural synaptic plasticity.
authors: Department of Biology, Stanford University, CA 94305, USA.
authors: Mikyoung
authors: M
authors: Park
authors: Shigeki
authors: S
authors: Watanabe
authors: Vivian Yi Nuo
authors: VY
authors: Poon
authors: Chan-Yen
authors: CY
authors: Ou
authors: Erik M
authors: EM
authors: Jorgensen
authors: Kang
authors: K
authors: Shen
references: Mol Biol Cell. 2004 Aug;15(8):3729-39
references: 15155810
references: Nature. 1998 Sep 3;395(6697):78-82
references: 9738501
references: Methods Cell Biol. 1995;48:451-82
references: 8531738
references: Cell Cycle. 2008 Nov 15;7(22):3487-90
references: 19001851
references: Curr Opin Cell Biol. 2001 Feb;13(1):36-40
references: 11163131
references: Neuron. 2006 Apr 6;50(1):13-8
references: 16600851
references: Nat Neurosci. 2007 Aug;10(8):980-9
references: 17643120
references: Nat Cell Biol. 2008 Nov;10(11):1269-79
references: 18849981
references: Neuron. 2008 May 22;58(4):571-83
references: 18498738
references: PLoS Genet. 2008 Nov;4(11):e1000283
references: 19043554
references: Neuron. 2003 Oct 9;40(2):243-64
references: 14556707
references: Cell. 1991 May 31;65(5):837-47
references: 1710172
references: J Neurosci. 2004 Apr 21;24(16):3907-16
references: 15102906
references: J Neurosci. 2006 Mar 29;26(13):3594-603
references: 16571768
references: Cell. 2007 Aug 24;130(4):704-16
references: 17719547
references: Nature. 1994 Dec 8;372(6506):519-24
references: 7990923
references: Nature. 1978 Feb 23;271(5647):764-6
references: 625347
references: Biochim Biophys Acta. 2009 Aug;1792(8):741-5
references: 19442718
references: Cell. 2008 Nov 28;135(5):960-73
references: 19041756
references: Genes Dev. 1987 Jun;1(4):398-414
references: 3678829
references: J Comp Neurol. 2004 Aug 2;475(4):540-50
references: 15236235
references: Mol Biol Cell. 2006 Jun;17(6):2617-25
references: 16571673
references: Annu Rev Neurosci. 1999;22:389-442
references: 10202544
references: J Neurosci. 2003 Apr 1;23(7):2591-9
references: 12684444
references: Nat Biotechnol. 2006 Apr;24(4):461-5
references: 16550175
references: Curr Opin Neurobiol. 2001 Feb;11(1):118-26
references: 11179881
references: Nat Neurosci. 2004 Apr;7(4):327-32
references: 15048120
references: Trends Genet. 1994 Apr;10(4):123-7
references: 8029828
references: J Neurosci. 2007 Jul 4;27(27):7284-96
references: 17611281
references: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18567-71
references: 19017796
references: Biotechnol J. 2007 Aug;2(8):949-57
references: 17526057
references: Curr Opin Neurobiol. 2000 Jun;10(3):303-11
references: 10851170
references: Science. 1984 Oct 26;226(4673):409-16
references: 6494891
references: Neuron. 2000 Feb;25(2):269-78
references: 10719884
references: Proc Natl Acad Sci U S A. 2004 May 18;101(20):7805-8
references: 15136720
references: Curr Opin Neurobiol. 2002 Feb;12(1):93-9
references: 11861170
references: Nature. 2002 Dec 19-26;420(6917):788-94
references: 12490942
references: Cell. 2010 May 28;141(5):846-58
references: 20510931
references: Nat Biotechnol. 2004 Nov;22(11):1374-6
references: 15529159
references: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12651-6
references: 12271129
references: Neuron. 2005 Dec 8;48(5):825-38
references: 16337919