PXD040331 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Altered striatal actin - dynamics drives behavioral inflexibility in a mouse model of Fragile X syndrome |
Description | The proteome of glutamatergic synapses is diverse across the mammalian brain and involved in neurodevelopmental disorders (NDDs). Among those is Fragile X syndrome (FXS), an NDD caused by the dysfunctional RNA binding protein FMRP. Here we demonstrate how the brain region-specific composition of post-synaptic density (PSD) contributes to FXS. The FXS mouse model shows, in the striatum, an altered association of the PSD with the actin cytoskeleton, reflecting immature dendritic spine morphology and reduced synaptic actin dynamics. Enhancing actin turnover with constitutively active RAC1 ameliorates these deficits. At the behavioral level, the FXS model displays striatal-driven inflexibility, a typical feature of FXS individuals, that is rescued by exogenous RAC1. Striatal ablation of Fmr1 is sufficient to recapitulate behavioral impairments observed in the FXS model. These results indicate that dysregulation of synaptic actin dynamics in the striatum, a region largely unexplored in FXS, contributes to the manifestation of FXS behavioral phenotypes. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:47:24.877.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Tilmann Achsel |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-02-22 10:17:06 | ID requested | |
1 | 2023-06-08 09:21:29 | announced | |
2 | 2023-11-14 08:48:36 | announced | 2023-11-14: Updated project metadata. |
⏵ 3 | 2024-10-22 05:47:25 | announced | 2024-10-22: Updated project metadata. |
Publication List
Mercaldo V, Vidimova B, Gastaldo D, Fern, á, ndez E, Lo AC, Cencelli G, Pedini G, De Rubeis S, Longo F, Klann E, Smit AB, Grant SGN, Achsel T, Bagni C, Altered striatal actin dynamics drives behavioral inflexibility in a mouse model of fragile X syndrome. Neuron, 111(11):1760-1775.e8(2023) [pubmed] |
10.1016/j.neuron.2023.03.008; |
Keyword List
submitter keyword: Fmr1(y/ -), hippocampus, striatum, actin, cortex,post-synaptic density |
Contact List
Claudia Bagni |
contact affiliation | Department of Fundamental Neurosciences, Université de Lausanne, 1005 Lausanne, Switzerland & Department of Biomedicine and Prevention, Università degli studi di Roma "Tor Vergata", 00133 Rome, Italy |
contact email | Claudia.Bagni@unil.ch |
lab head | |
Tilmann Achsel |
contact affiliation | Dept. of Fundamental Neurosciences University of Lausanne |
contact email | Tilmann.Achsel@unil.ch |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD040331
- Label: PRIDE project
- Name: Altered striatal actin - dynamics drives behavioral inflexibility in a mouse model of Fragile X syndrome