A Functional Role of Postsynaptic Density-95-Guanylate Kinase-Associated Protein Complex in Regulating Shank Assembly and Stability to Synapses

Romorini, Stefano; Piccoli, Giovanni; Jiang, Ming; Grossano, Pasquale; Tonna, Noemi; Passafaro, Maria; Zhang, Mingjie; Sala, Carlo

doi:10.1523/jneurosci.3314-04.2004

Cited by 83 publications

(78 citation statements)

References 59 publications

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“…Single transfections of these constructs revealed punctate and fibrillar staining patterns reflecting the intracellular localization of these proteins upon overexpression as previously described (Romorini et al, 2004;Thyssen et al, 2006;Proepper et al, 2007;Schmeisser et al, 2009;Grabrucker et al, 2011) (Supp. Fig.…”

Section: Lapser1 Interacts and Colocalizes With All Three Members Of supporting

confidence: 57%

The spatio‐temporal expression of ProSAP/shank family members and their interaction partner LAPSER1 during Xenopus laevis development

Gessert¹,

Schmeißer²,

Si³

et al. 2011

Developmental Dynamics

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Members of the ProSAP/Shank family are important scaffolding proteins of the postsynaptic density (PSD). We investigated for the first time the expression of the three family members named Shank1, ProSAP1/Shank2, and ProSAP2/Shank3 during Xenopus laevis development. Shank1 is expressed in the neural tube, the retina, and the cranial ganglions. In contrast, ProSAP1/Shank2 transcripts could be visualized in the otic vesicle, the pronephros, the liver, the neural tube, and the retina. ProSAP2/Shank3 could be detected in the cardiovascular network, the neural tube, the pronephros, and the retina. Furthermore, we showed that LAPSER1 interacts with all three ProSAP/Shank family members in Xenopus embryos and co‐localizes with ProSAP/Shank in a cell‐based assay. In Xenopus, LAPSER1 is expressed in somites, brain, proctodeum, pronephros, and in some cranial ganglions. Thus, we suggest that members of the ProSAP/Shank family and LAPSER1 not only play a role in PSD formation and plasticity, but also during embryonic development. Developmental Dynamics 240:1528–1536, 2011. © 2011 Wiley‐Liss, Inc.

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Section: Lapser1 Interacts and Colocalizes With All Three Members Of supporting

confidence: 57%

The spatio‐temporal expression of ProSAP/shank family members and their interaction partner LAPSER1 during Xenopus laevis development

Gessert¹,

Schmeißer²,

Si³

et al. 2011

Developmental Dynamics

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“…High throughput techniques have revealed that the encoded proteins of many suspected ASD genes are located at the postsynaptic density, making this pathway a hotspot for ASD-causing mutations. At postsynaptic density, DLGAP2 could be an adapter component linking ion channels to the subsynaptic cytoskeleton in interactions with the scaffolding SHANK2 and SHANK3 proteins, which are key players in ASD pathophysiology [2,27,28]. DLGAP2 is a direct binding partner of the NRXN/NLGN/ SHANK protein complex, one of the first pathways to emerge in the etiology of ASD.…”

Section: Discussionmentioning

confidence: 99%

Further Evidence for Dlgap2 as Strong Autism Spectrum Disorders/Intellectual Disability Candidate Gene

Poquet¹,

Faivre²,

Chehadeh³

et al. 2017

Autism Open Access

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Autism spectrum disorders are classified as neurodevelopmental disorders characterised by diminished social communication and interaction. The core symptoms typically coexist with other medical conditions such as intellectual disability. The involvement of rare copy number variations of varying expressivity and penetrance as risk factors in autism spectrum disorders/intellectual disability phenotypes has been highlighted in large series. The DLGAP2 gene, whose glutamatergic postsynaptic density product may play a role in synaptogenesis and plasticity, has been identified as a novel candidate on the basis of 2 de novo duplications in sporadic non-syndromic autism spectrum disorders/intellectual disability males. It has also been suggested that increased DLGAP2 gene expression may contribute to the pathogenesis of schizophrenia spectrum disorders. Based on these results and after fine phenotyping of another patient with a de novo duplication involving DLGAP2 and presenting with autism spectrum disorder intersecting early-onset schizophrenia spectrum disorder, we gathered an international series of 9 cases (6 families) via international data sharing. Four sporadic males presented with autism spectrum disorders and one had other neurodevelopmental disorders. A family with 4 females displayed intellectual disability (2/4) and specific learning disorder (2/4). This study supports the hypothesis that rare copy number variations encompassing DLGAP2 with incomplete penetrance and variable expressivity could predispose to a broad range of early-onset neurodevelopmental disorders trajectories including autism spectrum disorders/intellectual disability, highlighting the existence of common predisposing factors to these overlapping phenotypic spectrums.

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“…Hippocampal neuron cultures were prepared from 18-to 19-d-old rat embryos from Charles River. High-density (750 -1000 cells/mm 2 ) and medium-density (150 -200 cells/mm 2 ) neurons were plated and grown as described by (Romorini et al, 2004) using home-made B27. Neurons were plated onto 6-well plastic tissue culture plates (Iwaki, Bibby Sterilin) or 18 mm diameter coverslips, and grown on 12-well plastic tissue culture plates (Iwaki).…”

Section: Methodsmentioning

confidence: 99%

“…The clusters, localized at the dendrites of transfected neurons, were counted manually using the merge images and divided in two categories, those localized at dendritic protrusions and those not. The percentage of clusters localized at dendritic protrusions relative to total was then calculated (Sala et al, 2001;Romorini et al, 2004). All measurements were expressed means Ϯ SEM.…”

Section: Methodsmentioning

confidence: 99%

Synaptic Activity Controls Dendritic Spine Morphology by Modulating eEF2-Dependent BDNF Synthesis

Verpelli

Piccoli²,

Zibetti³

et al. 2010

J. Neurosci.

136

120

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Activity-dependent changes in synaptic structure and spine morphology are required for learning and memory, and depend on protein translation. We show that the kinase for eukaryotic elongation factor 2 (eEF2K) regulates dendritic spine stability and synaptic structure by modulating activity-dependent dendritic BDNF synthesis. Specifically RNAi knockdown of eEF2K reduces dendritic spine stability and inhibits dendritic BDNF protein expression; whereas overexpression of a constitutively activated eEF2K induces spine maturation and increases expression of dendritic BDNF. Furthermore, BDNF overexpression rescues the spine stability reduced by RNAi knockdown of eEF2K. We also show that synaptic activity-dependent spine maturation and dendritic BDNF protein expression depend on mGluR/EF2K-induced eEF2 phosphorylation. We propose that the eEF2K/eEF2 pathway is a key biochemical sensor that couple neuronal activity to spine plasticity, by controlling the dendritic translation of BDNF.

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A Functional Role of Postsynaptic Density-95-Guanylate Kinase-Associated Protein Complex in Regulating Shank Assembly and Stability to Synapses

Cited by 83 publications

References 59 publications

The spatio‐temporal expression of ProSAP/shank family members and their interaction partner LAPSER1 during Xenopus laevis development

The spatio‐temporal expression of ProSAP/shank family members and their interaction partner LAPSER1 during Xenopus laevis development

Further Evidence for Dlgap2 as Strong Autism Spectrum Disorders/Intellectual Disability Candidate Gene

Synaptic Activity Controls Dendritic Spine Morphology by Modulating eEF2-Dependent BDNF Synthesis

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