Clozapine and haloperidol differentially regulate dendritic spine formation and synaptogenesis in rat hippocampal neurons

2006 ◽  
Vol 32 (4) ◽  
pp. 356-365 ◽  
Author(s):  
H.M. Critchlow ◽  
P.R. Maycox ◽  
J.N. Skepper ◽  
O. Krylova
Keyword(s):  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Spine Formation

scholarly journals Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation

2013 ◽  
Vol 24 (10) ◽  
pp. 1602-1613 ◽  
Author(s):  
Shuhei Ueda ◽  
Manabu Negishi ◽  
Hironori Katoh
Keyword(s):  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Actin Binding ◽  
Spine Density ◽  
Nucleotide Exchange ◽  
Spine Formation ◽  
Nucleotide Exchange Factor ◽  
Important Interaction

In neuronal development, dendritic spine formation is important for the establishment of excitatory synaptic connectivity and functional neural circuits. Developmental deficiency in spine formation results in multiple neuropsychiatric disorders. Dock4, a guanine nucleotide exchange factor (GEF) for Rac, has been reported as a candidate genetic risk factor for autism, dyslexia, and schizophrenia. We previously showed that Dock4 is expressed in hippocampal neurons. However, the functions of Dock4 in hippocampal neurons and the underlying molecular mechanisms are poorly understood. Here we show that Dock4 is highly concentrated in dendritic spines and implicated in spine formation via interaction with the actin-binding protein cortactin. In cultured neurons, short hairpin RNA (shRNA)–mediated knockdown of Dock4 reduces dendritic spine density, which is rescued by coexpression of shRNA-resistant wild-type Dock4 but not by a GEF-deficient mutant of Dock4 or a truncated mutant lacking the cortactin-binding region. On the other hand, knockdown of cortactin suppresses Dock4-mediated spine formation. Taken together, the results show a novel and functionally important interaction between Dock4 and cortactin for regulating dendritic spine formation via activation of Rac.

The Rac activator Dock4 regulates dendritic spine formation in hippocampal neurons

2011 ◽  
Vol 71 ◽  
pp. e336
Author(s):  
Shuhei Ueda ◽  
Manabu Negishi ◽  
Hironori Katoh
Keyword(s):  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Spine Formation

Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons

2005 ◽  
Vol 8 (2) ◽  
pp. 164-172 ◽  
Author(s):  
Yuanyuan Ji ◽  
Petti T Pang ◽  
Linyin Feng ◽  
Bai Lu
Keyword(s):  
Cyclic Amp ◽  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Spine Formation

scholarly journals Autism-linked mutations of CTTNBP2 reduce social interaction and impair dendritic spine formation via diverse mechanisms

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Pu-Yun Shih ◽  
Bing-Yuan Hsieh ◽  
Ching-Yen Tsai ◽  
Chiu-An Lo ◽  
Brian E. Chen ◽  
...  
Keyword(s):  
Social Interaction ◽  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Short Form ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Spine Density ◽  
Spine Formation ◽  
Molecular Features

Abstract Abnormal synaptic formation and signaling is one of the key molecular features of autism spectrum disorders (ASD). Cortactin binding protein 2 (CTTNBP2), an ASD-linked gene, is known to regulate the subcellular distribution of synaptic proteins, such as cortactin, thereby controlling dendritic spine formation and maintenance. However, it remains unclear how ASD-linked mutations of CTTNBP2 influence its function. Here, using cultured hippocampal neurons and knockin mouse models, we screen seven ASD-linked mutations in the short form of the Cttnbp2 gene and identify that M120I, R533* and D570Y mutations impair CTTNBP2 protein–protein interactions via divergent mechanisms to reduce dendritic spine density in neurons. R533* mutation impairs CTTNBP2 interaction with cortactin due to lack of the C-terminal proline-rich domain. Through an N–C terminal interaction, M120I mutation at the N-terminal region of CTTNBP2 also negatively influences cortactin interaction. D570Y mutation increases the association of CTTNBP2 with microtubule, resulting in a dendritic localization of CTTNBP2, consequently reducing the distribution of CTTNBP2 in dendritic spines and impairing the synaptic function of CTTNBP2. Finally, we generated heterozygous M120I knockin mice to mimic the genetic variation of patients and found they exhibit reduced social interaction. Our study elucidates that different ASD-linked mutations of CTTNBP2 result in diverse molecular deficits, but all have the similar consequence of synaptic impairment.

scholarly journals Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus

2003 ◽  
Vol 163 (6) ◽  
pp. 1313-1326 ◽  
Author(s):  
Mark Henkemeyer ◽  
Olga S. Itkis ◽  
Michelle Ngo ◽  
Peter W. Hickmott ◽  
Iryna M. Ethell
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Tyrosine Kinases ◽  
Hippocampal Neurons ◽  
Receptor Tyrosine Kinases ◽  
Triple Mutant ◽  
Spine Formation ◽  
Truncating Mutation ◽  
Ephb Receptor ◽  
Spine Development

Here, using a genetic approach, we dissect the roles of EphB receptor tyrosine kinases in dendritic spine development. Analysis of EphB1, EphB2, and EphB3 double and triple mutant mice lacking these receptors in different combinations indicates that all three, although to varying degrees, are involved in dendritic spine morphogenesis and synapse formation in the hippocampus. Hippocampal neurons lacking EphB expression fail to form dendritic spines in vitro and they develop abnormal spines in vivo. Defective spine formation in the mutants is associated with a drastic reduction in excitatory glutamatergic synapses and the clustering of NMDA and AMPA receptors. We show further that a kinase-defective, truncating mutation in EphB2 also results in abnormal spine development and that ephrin-B2–mediated activation of the EphB receptors accelerates dendritic spine development. These results indicate EphB receptor cell autonomous forward signaling is responsible for dendritic spine formation and synaptic maturation in hippocampal neurons.

scholarly journals The F-BAR Protein Rapostlin Regulates Dendritic Spine Formation in Hippocampal Neurons

2011 ◽  
Vol 286 (37) ◽  
pp. 32672-32683 ◽  
Author(s):  
Yohei Wakita ◽  
Tetsuhiro Kakimoto ◽  
Hironori Katoh ◽  
Manabu Negishi
Keyword(s):  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Spine Formation

scholarly journals A Role of Rnd1 GTPase in Dendritic Spine Formation in Hippocampal Neurons

2003 ◽  
Vol 23 (35) ◽  
pp. 11065-11072 ◽  
Author(s):  
Yukio Ishikawa ◽  
Hironori Katoh ◽  
Manabu Negishi
Keyword(s):  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Spine Formation

The F-BAR protein Rapostlin regulates endocytosis and dendritic spine formation in hippocampal neurons

2011 ◽  
Vol 71 ◽  
pp. e135
Author(s):  
Yohei Wakita ◽  
Tetsuhiro Kakimoto ◽  
Hironori Katoh ◽  
Manabu Negishi
Keyword(s):  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Spine Formation
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