PXD040331

PXD040331 is an original dataset announced via ProteomeXchange.

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

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.

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;

submitter keyword: Fmr1(y/ -), hippocampus, striatum, actin, cortex,post-synaptic density

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/06/PXD040331

PRIDE project URI

• PRIDE
  1. PXD040331
     1. Label: PRIDE project
     2. Name: Altered striatal actin - dynamics drives behavioral inflexibility in a mouse model of Fragile X syndrome