Neural Cell Adhesion Molecule NrCAM Regulates Semaphorin 3F-Induced Dendritic Spine Remodeling

被引:59
作者
Demyanenko, Galina P. [1 ]
Mohan, Vishwa [1 ]
Zhang, Xuying [1 ]
Brennaman, Leann H. [1 ]
Dharbal, Katherine E. S. [1 ]
Tran, Tracy S. [4 ]
Manis, Paul B. [2 ,3 ]
Maness, Patricia F. [1 ]
机构
[1] Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Sch Med, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA
[4] Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA
基金
美国国家卫生研究院;
关键词
cell adhesion; cortical pyramidal neurons; NrCAM; semaphorin; spine morphogenesis; visual cortex; PRIMARY VISUAL-CORTEX; AUTISM SPECTRUM DISORDERS; NR-CAM; HOMOPHILIC INTERACTION; THALAMOCORTICAL AXONS; FUNCTIONAL PLASTICITY; ASSOCIATION ANALYSIS; MOUSE; EXPERIENCE; BRAIN;
D O I
10.1523/JNEUROSCI.1774-14.2014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Neuron-glial related cell adhesion molecule (NrCAM) is a regulator of axon growth and repellent guidance, and has been implicated in autism spectrum disorders. Here a novel postsynaptic role for NrCAM in Semaphorin3F (Sema3F)-induced dendritic spine remodeling was identified in pyramidal neurons of the primary visual cortex (V1). NrCAM localized to dendritic spines of star pyramidal cells in postnatal V1, where it was coexpressed with Sema3F. NrCAM deletion in mice resulted in elevated spine densities on apical dendrites of star pyramidal cells at both postnatal and adult stages, and electron microscopy revealed increased numbers of asymmetric synapses in layer 4 of V1. Whole-cell recordings in cortical slices from NrCAM-null mice revealed increased frequency of mEPSCs in star pyramidal neurons. Recombinant Sema3F-Fc protein induced spine retraction on apical dendrites of wild-type, but not NrCAM-null cortical neurons in culture, while re-expression ofNrCAM rescued the spine retraction response. NrCAM formed a complex in brain with Sema3F receptor subunits Neuropilin-2 (Npn-2) and PlexinA3 (PlexA3) through an Npn-2-binding sequence (TARNER) in the extracellular Igl domain. A trans heterozygous genetic interaction test demonstrated that Sema3F and NrCAM pathways interacted in vivo to regulate spine density in star pyramidal neurons. These findings reveal NrCAM as a novel postnatal regulator of dendritic spine density in cortical pyramidal neurons, and an integral component of the Sema3F receptor complex. The results implicate NrCAM as a contributor to excitatory/inhibitory balance in neocortical circuits.
引用
收藏
页码:11274 / 11287
页数:14
相关论文
共 78 条
[1]   POLYNEURONAL INNERVATION OF SPINY STELLATE NEURONS IN CAT VISUAL-CORTEX [J].
AHMED, B ;
ANDERSON, JC ;
DOUGLAS, RJ ;
MARTIN, KAC ;
NELSON, JC .
JOURNAL OF COMPARATIVE NEUROLOGY, 1994, 341 (01) :39-49
[2]   Anatomical and physiological plasticity of dendritic spines [J].
Alvarez, Veronica A. ;
Sabatini, Bernardo L. .
ANNUAL REVIEW OF NEUROSCIENCE, 2007, 30 :79-97
[3]  
Antonini A, 1999, J NEUROSCI, V19, P4388
[4]   Outline structure of the human L1 cell adhesion molecule and the sites where mutations cause neurological disorders [J].
Bateman, A ;
Jouet, M ;
MacFarlane, J ;
Du, JS ;
Kenwrick, S ;
Chothia, C .
EMBO JOURNAL, 1996, 15 (22) :6050-6059
[5]   A quantitative map of the circuit of cat primary visual cortex [J].
Binzegger, T ;
Douglas, RJ ;
Martin, KAC .
JOURNAL OF NEUROSCIENCE, 2004, 24 (39) :8441-8453
[6]   Mutation screening and association analysis of six candidate genes for autism on chromosome 7q [J].
Bonora, E ;
Lamb, JA ;
Barnby, G ;
Sykes, N ;
Moberly, T ;
Beyer, KS ;
Klauck, SM ;
Poustka, F ;
Bacchelli, E ;
Blasi, F ;
Maestrini, E ;
Battaglia, A ;
Haracopos, D ;
Pedersen, L ;
Isager, T ;
Eriksen, G ;
Viskum, B ;
Sorensen, EU ;
Brondum-Nielsen, K ;
Cotterill, R ;
von Engeland, H ;
de Jonge, M ;
Kemner, C ;
Steggehuis, K ;
Scherpenisse, M ;
Rutter, M ;
Bolton, PF ;
Parr, JR ;
Poustka, A ;
Bailey, AJ ;
Monaco, AP .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2005, 13 (02) :198-207
[7]   Epilepsy and autism spectrum disorders: Are there common developmental mechanisms? [J].
Brooks-Kayal, Amy .
BRAIN & DEVELOPMENT, 2010, 32 (09) :731-738
[8]  
Castellani V, 2002, ADV EXP MED BIOL, V515, P91
[9]   THE RAT-BRAIN POSTSYNAPTIC DENSITY FRACTION CONTAINS A HOMOLOG OF THE DROSOPHILA DISKS-LARGE TUMOR SUPPRESSOR PROTEIN [J].
CHO, KO ;
HUNT, CA ;
KENNEDY, MB .
NEURON, 1992, 9 (05) :929-942
[10]   RETINOID SIGNALING AND THE GENERATION OF REGIONAL AND CELLULAR DIVERSITY IN THE EMBRYONIC MOUSE SPINAL-CORD [J].
COLBERT, MC ;
RUBIN, WW ;
LINNEY, E ;
LAMANTIA, AS .
DEVELOPMENTAL DYNAMICS, 1995, 204 (01) :1-12