Regulation of dendritic spine morphology by SPIN90, a novel Shank binding partner

Kim, Seon-Myung; Choi, Kyu Yeong; Cho, In Ha; Rhy, Jin Hee; Kim, Sung Hyun; Park, Chul–Seung; Kim, Eunjoon; Song, Woo Keun

doi:10.1111/j.1471-4159.2009.06039.x

Cited by 20 publications

(23 citation statements)

References 51 publications

(78 reference statements)

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“…The specific function of Shank proteins in dendritic spines is probably related to the fact that all three protein variants bind directly to a number of proteins involved in actin remodeling, such as cortactin, Abp1, IRsP53, and SPIN90 (11, 42–44); they also interact indirectly with actin-remodeling proteins through binding Homer, oligophrenin, and CdC42 (45, 46). Available data suggest that Shank proteins functionally link glutamate receptors to the cytoskeleton, thereby regulating the size and dimensions of excitatory synapses and dendritic spines (47).…”

Section: Discussionmentioning

confidence: 99%

Importance of Shank3 Protein in Regulating Metabotropic Glutamate Receptor 5 (mGluR5) Expression and Signaling at Synapses

Verpelli

Dvoretskova

Vicidomini

et al. 2011

Journal of Biological Chemistry

187

183

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Shank3/PROSAP2 gene mutations are associated with cognitive impairment ranging from mental retardation to autism. Shank3 is a large scaffold postsynaptic density protein implicated in dendritic spines and synapse formation; however, its specific functions have not been clearly demonstrated. We have used RNAi to knockdown Shank3 expression in neuronal cultures and showed that this treatment specifically reduced the synaptic expression of the metabotropic glutamate receptor 5 (mGluR5), but did not affect the expression of other major synaptic proteins. The functional consequence of Shank3 RNAi knockdown was impaired signaling via mGluR5, as shown by reduction in ERK1/2 and CREB phosphorylation induced by stimulation with (S)-3,5-dihydroxyphenylglycine (DHPG) as the agonist of mGluR5 receptors, impaired mGluR5-dependent synaptic plasticity (DHPG-induced long-term depression), and impaired mGluR5-dependent modulation of neural network activity. We also found morphological abnormalities in the structure of synapses (spine number, width, and length) and impaired glutamatergic synaptic transmission, as shown by reduction in the frequency of miniature excitatory postsynaptic currents (mEPSC). Notably, pharmacological augmentation of mGluR5 activity using 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)-benzamide as the positive allosteric modulator of these receptors restored mGluR5-dependent signaling (DHPG-induced phosphorylation of ERK1/2) and normalized the frequency of mEPSCs in Shank3-knocked down neurons. These data demonstrate that a deficit in mGluR5-mediated intracellular signaling in Shank3 knockdown neurons can be compensated by 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)-benzamide; this raises the possibility that pharmacological augmentation of mGluR5 activity represents a possible new therapeutic approach for patients with Shank3 mutations.

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Section: Discussionmentioning

confidence: 99%

Importance of Shank3 Protein in Regulating Metabotropic Glutamate Receptor 5 (mGluR5) Expression and Signaling at Synapses

Verpelli

Dvoretskova

Vicidomini

et al. 2011

Journal of Biological Chemistry

187

183

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“…Shank proteins (Shank1-3) are scaffolding molecules of the postsynaptic density (PSD) of excitatory synapses, which are crucial for PSD assembly and the formation of dendritic spines. Shank1 mRNAs are distinguished by their translational regulation [Falley et al, 2009] and Shank1b, together with specific binding partners, acts as a key contributor to the regulation of dendritic spine morphogenesis and brain function [Kim et al, 2009]. SHANK3 codes for a scaffolding protein of the PSD that binds to neuroligins and regulates the size and shape of dendritic spines [Roussignol et al, 2005].…”

Section: Discussionmentioning

confidence: 99%

Olfactory Receptor-Related Duplicons Mediate a Microdeletion at 11q13.2q13.4 Associated with a Syndromic Phenotype

Wischmeijer¹,

Magini²,

Giorda

et al. 2010

Mol Syndromol

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By array-CGH, we identified a cryptic deletion of about 3.4 Mb involving the chromosomal region 11q13.2q13.4 in a child with speech and developmental delay. Highly homologous segmental duplications related to the well-known olfactory receptor (OR)-containing clusters at 8p and 4p are located at the breakpoints of the imbalance and may be involved in its occurrence. Although these structural features are known to promote recurrent chromosomal rearrangements and previous studies had included the 11q13.2q13.4 deletion region among those considered potentially more unstable, neither deletions nor duplications of this region had been reported until now. Among the deleted genes, SHANK2 might play a role in the phenotype of the patient since it encodes a postsynaptic scaffolding protein similar to SHANK3, whose haploinsufficiency is a well-known cause of severe speech delay and autistic-like behavior, and recently deletions and mutations of SHANK2 have been described in patients with an autistic spectrum disorder or mental retardation.

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“…DIP reportedly directly binds and activates the Arp2/3 complex, although this was not confirmed in cells [20]. The DIP knockout mouse showed slight diminution of actin accumulation in dendritic spines on explanted neurons [26], enhanced synaptic functions and motor function testing, and impaired MEF migration [27], [28].…”

Section: Introductionmentioning

confidence: 99%

Dia-Interacting Protein (DIP) Imposes Migratory Plasticity in mDia2-Dependent Tumor Cells in Three-Dimensional Matrices

et al. 2012

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Tumor cells rely upon membrane pliancy to escape primary lesions and invade secondary metastatic sites. This process relies upon localized assembly and disassembly cycles of F-actin that support and underlie the plasma membrane. Dynamic actin generates both spear-like and bleb structures respectively characterizing mesenchymal and amoeboid motility programs utilized by metastatic cells in three-dimensional matrices. The molecular mechanism and physiological trigger(s) driving membrane plasticity are poorly understood. mDia formins are F-actin assembly factors directing membrane pliancy in motile cells. mDia2 is functionally coupled with its binding partner DIP, regulating cortical actin and inducing membrane blebbing in amoeboid cells. Here we show that mDia2 and DIP co-tether to nascent blebs and this linkage is required for bleb formation. DIP controls mesenchymal/amoeboid cell interconvertability, while CXCL12 induces assembly of mDia2:DIP complexes to bleb cortices in 3D matrices. These results demonstrate how DIP-directed mDia2-dependent F-actin dynamics regulate morphological plasticity in motile cancer cells.

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Regulation of dendritic spine morphology by SPIN90, a novel Shank binding partner

Cited by 20 publications

References 51 publications

Importance of Shank3 Protein in Regulating Metabotropic Glutamate Receptor 5 (mGluR5) Expression and Signaling at Synapses

Importance of Shank3 Protein in Regulating Metabotropic Glutamate Receptor 5 (mGluR5) Expression and Signaling at Synapses

Olfactory Receptor-Related Duplicons Mediate a Microdeletion at 11q13.2q13.4 Associated with a Syndromic Phenotype

Dia-Interacting Protein (DIP) Imposes Migratory Plasticity in mDia2-Dependent Tumor Cells in Three-Dimensional Matrices

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