A functional role of postsynaptic density-95-guanylate kinase-associated protein complex in regulating Shank assembly and stability to synapses.
- Authors
- Romorini, Stefano; Piccoli, Giovanni; Jiang, Ming; Grossano, Pasquale; Tonna, Noemi; Passafaro, Maria; Zhang, Mingjie; Sala, Carlo
- Year
- 2004
- Journal
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- PMID
- 15496675
- DOI
- 10.1523/JNEUROSCI.3314-04.2004
- PMCID
- PMC6730104
Postsynaptic density (PSD) proteins include scaffold, cytoskeletal, and signaling proteins that structurally and functionally interact with glutamate receptors and other postsynaptic membrane proteins. The molecular mechanisms regulating the assembly of PSD proteins and their associations with synapses are still widely unknown. We investigated the molecular mechanisms of Shank1 targeting and synapse assembly by looking at the function of guanylate kinase-associated protein (GKAP) and PSD-95 interactions. Shank1 when it is not associated to GKAP, which binds to the Shank PSD-95-Discs Large-zona occludens-1 domain, forms filamentous and fusiform structures in which the Src homology 3 domain specifically interacts with the ankyrin repeat domain, thus allowing its multimerization via a novel form of intermolecular interaction. Surprisingly, in both COS-7 cells and hippocampal neurons, GKAP forms insoluble aggregates with Shank that colocalize with heat shock protein 70 and neurofilaments, two markers of the aggresomes in which misfolded proteins accumulate. However, the two proteins are organized in clusters in COS cells and synaptic clusters in neurons when both are overexpressed and associated with wild-type PSD-95, but not with palmitoylation-deficient PSD-95. Synaptic activity in neurons induces the formation of Shank and GKAP intracellular aggregation and degradation. Similarly, the overexpression of a GKAP mutant that is incapable of binding PSD-95 induces Shank aggregation and degradation in neurons. Our data suggest a possible functional and structural role of the PSD-95-GKAP complex in Shank and PSD protein assembly and stability to synapses.
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| Title | Year | PMID |
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Long Term High-Salt Diet Induces Cognitive Impairments via Down-Regulating SHANK1. | Guo C et al. | β | 2025 | β |
| Sel1l May Contributes to the Determinants of Neuronal Lineage and Neuronal Maturation Regardless of Hrd1 via Atf6-Sel1l Signaling. | Saito R et al. | β | 2023 | β |
| Molecular physiology of Arc/Arg3.1: The oligomeric state hypothesis of synaptic plasticity. | Eriksen MS et al. | β | 2022 | β |
| POSH regulates assembly of the NMDAR/PSD-95/Shank complex and synaptic function. | Yao M et al. | β | 2022 | β |
| SAPAP Scaffold Proteins: From Synaptic Function to Neuropsychiatric Disorders. | Bai Y et al. | β | 2022 | β |
| SHANK3 Antibody Validation: Differential Performance in Western Blotting, Immunocyto- and Immunohistochemistry. | Lutz AK et al. | β | 2022 | β |
| SHANK family on stem cell fate and development. | Liu X et al. | β | 2022 | β |
| The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders. | Lee K et al. | β | 2022 | β |
| Comparison of SHANK3 deficiency in animal models: phenotypes, treatment strategies, and translational implications. | Delling JP et al. | β | 2021 | β |
| Role of actin cytoskeleton in the organization and function of ionotropic glutamate receptors. | Dutta P et al. | β | 2021 | β |
| Structural properties and peptide ligand binding of the capsid homology domains of human Arc. | Hallin EI et al. | β | 2021 | β |
| Truncating variants in the SHANK1 gene are associated with a spectrum of neurodevelopmental disorders. | May HJ et al. | β | 2021 | β |
| Altered synaptic ultrastructure in the prefrontal cortex of Shank3-deficient rats. | Jacot-Descombes S et al. | β | 2020 | β |
| LSD1 is an environmental stress-sensitive negative modulator of the glutamatergic synapse. | Longaretti A et al. | β | 2020 | β |
| Shanks - multidomain molecular scaffolds of the postsynaptic density. | Kursula P | β | 2019 | β |
| Cell-Type-Specific <i>Shank2</i> Deletion in Mice Leads to Differential Synaptic and Behavioral Phenotypes. | Kim R et al. | β | 2018 | β |
| Solution structures of the SH3 domains from Shank scaffold proteins and their interactions with Cav1.3 calcium channels. | Ishida H et al. | β | 2018 | β |
| De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome. | Sagar A et al. | β | 2017 | β |
| Shank Proteins Differentially Regulate Synaptic Transmission. | Shi R et al. | β | 2017 | β |
| Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs. | Zhu J et al. | β | 2017 | β |
| The DLGAP family: neuronal expression, function and role in brain disorders. | Rasmussen AH et al. | β | 2017 | β |
| The X-Linked Intellectual Disability Protein IL1RAPL1 Regulates Dendrite Complexity. | Montani C et al. | β | 2017 | β |
| Selective Localization of Shanks to VGLUT1-Positive Excitatory Synapses in the Mouse Hippocampus. | Heise C et al. | β | 2016 | β |
| NOMA-GAP/ARHGAP33 regulates synapse development and autistic-like behavior in the mouse. | Schuster S et al. | β | 2015 | β |
| Shank synaptic scaffold proteins: keys to understanding the pathogenesis of autism and other synaptic disorders. | Sala C et al. | β | 2015 | β |
| A non-canonical initiation site is required for efficient translation of the dendritically localized Shank1 mRNA. | Studtmann K et al. | β | 2014 | β |
| Elongation factor-2 phosphorylation in dendrites and the regulation of dendritic mRNA translation in neurons. | Heise C et al. | β | 2014 | β |
| Phosphorylation of neuronal Lysine-Specific Demethylase 1LSD1/KDM1A impairs transcriptional repression by regulating interaction with CoREST and histone deacetylases HDAC1/2. | Toffolo E et al. | β | 2014 | β |
| Synaptic basis of social dysfunction: a focus on postsynaptic proteins linking group-I mGluRs with AMPARs and NMDARs. | O'Connor EC et al. | β | 2014 | β |
| Comparative neuronal differentiation of self-renewing neural progenitor cell lines obtained from human induced pluripotent stem cells. | Verpelli C et al. | β | 2013 | β |
| Dances with black widow spiders: dysregulation of glutamate signalling enters centre stage in ADHD. | Lesch KP et al. | β | 2013 | β |
| Expression of cocaine-evoked synaptic plasticity by GluN3A-containing NMDA receptors. | Yuan T et al. | β | 2013 | β |
| Three cases of isolated terminal deletion of chromosome 8p without heart defects presenting with a mild phenotype. | Burnside RD et al. | β | 2013 | β |
| Altered balance of proteolytic isoforms of pro-brain-derived neurotrophic factor in autism. | Garcia KL et al. | β | 2012 | β |
| Calcium-dependent networks in dopamine-glutamate interaction: the role of postsynaptic scaffolding proteins. | de Bartolomeis A et al. | β | 2012 | β |
| GKAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling. | Shin SM et al. | β | 2012 | β |
| Roles of neuronal activity-induced gene products in Hebbian and homeostatic synaptic plasticity, tagging, and capture. | Hayashi Y et al. | β | 2012 | β |
| Scaffold proteins at the postsynaptic density. | Verpelli C et al. | β | 2012 | β |
| Serotonin in the modulation of neural plasticity and networks: implications for neurodevelopmental disorders. | Lesch KP et al. | β | 2012 | β |
| Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation. | Grabrucker AM et al. | β | 2011 | β |
| Importance of Shank3 protein in regulating metabotropic glutamate receptor 5 (mGluR5) expression and signaling at synapses. | Verpelli C et al. | β | 2011 | β |
| LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. | Piccoli G et al. | β | 2011 | β |
| Sapap3 deletion anomalously activates short-term endocannabinoid-mediated synaptic plasticity. | Chen M et al. | β | 2011 | β |
| The spatio-temporal expression of ProSAP/shank family members and their interaction partner LAPSER1 during Xenopus laevis development. | Gessert S et al. | β | 2011 | β |
| Alternative splicing of the histone demethylase LSD1/KDM1 contributes to the modulation of neurite morphogenesis in the mammalian nervous system. | Zibetti C et al. | β | 2010 | β |
| Degradation of postsynaptic scaffold GKAP and regulation of dendritic spine morphology by the TRIM3 ubiquitin ligase in rat hippocampal neurons. | Hung AY et al. | β | 2010 | β |
| Functional impact of global rare copy number variation in autism spectrum disorders. | Pinto D et al. | β | 2010 | β |
| Genome variation and complexity in the autism spectrum. | van de Lagemaat LN et al. | β | 2010 | β |
| Modulation of Shank3 PDZ domain ligand-binding affinity by dimerization. | Iskenderian-Epps WS et al. | β | 2010 | β |
| Synaptic activity controls dendritic spine morphology by modulating eEF2-dependent BDNF synthesis. | Verpelli C et al. | β | 2010 | β |
| Central sensitization: a generator of pain hypersensitivity by central neural plasticity. | Latremoliere A et al. | β | 2009 | β |
| Genome-wide detection and analysis of hippocampus core promoters using DeepCAGE. | Valen E et al. | β | 2009 | β |
| Receptor-associated proteins and synaptic plasticity. | Bruneau EG et al. | β | 2009 | β |
| Regulation of dendritic spine morphology by SPIN90, a novel Shank binding partner. | Kim SM et al. | β | 2009 | β |
| Shank1 mRNA: dendritic transport by kinesin and translational control by the 5'untranslated region. | Falley K et al. | β | 2009 | β |
| The postsynaptic density proteins Homer and Shank form a polymeric network structure. | Hayashi MK et al. | β | 2009 | β |
| Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions. | Wilson LS et al. | β | 2008 | β |
| HSP90 beta regulates rapsyn turnover and subsequent AChR cluster formation and maintenance. | Luo S et al. | β | 2008 | β |
| Scaffolding proteins at the postsynaptic density: shank as the architectural framework. | Kreienkamp HJ | β | 2008 | β |
| Synaptic adhesion molecules and PSD-95. | Han K et al. | β | 2008 | β |
| Proteomic analysis of activity-dependent synaptic plasticity in hippocampal neurons. | Piccoli G et al. | β | 2007 | β |
| A preformed complex of postsynaptic proteins is involved in excitatory synapse development. | Gerrow K et al. | β | 2006 | β |
| Local sharing as a predominant determinant of synaptic matrix molecular dynamics. | Tsuriel S et al. | β | 2006 | β |
| Molecular organization and assembly of the postsynaptic density of excitatory brain synapses. | Kim E et al. | β | 2006 | β |
| Structural modeling of protein interactions by analogy: application to PSD-95. | Korkin D et al. | β | 2006 | β |
| Key role of the postsynaptic density scaffold proteins Shank and Homer in the functional architecture of Ca2+ homeostasis at dendritic spines in hippocampal neurons. | Sala C et al. | β | 2005 | β |
| Molecular mechanisms of dendritic spine development and remodeling. | Ethell IM et al. | β | 2005 | β |
| Postsynaptic shank antagonizes dendrite branching induced by the leucine-rich repeat protein Densin-180. | Quitsch A et al. | β | 2005 | β |
| Shank expression is sufficient to induce functional dendritic spine synapses in aspiny neurons. | Roussignol G et al. | β | 2005 | β |