PXD029257

PXD029257 is an original dataset announced via ProteomeXchange.

Title	Astrocyte and neuron subcompartment proteomes reveal distinct cellular and molecular mechanisms of OCD
Description	Astrocytes and neurons coexist and interact in the CNS1,2. Given that many signaling and pathological events are protein-driven, identifying astrocyte and neuron proteomes is essential for elucidating the complex protein networks that dictate their respective contributions to physiology and disease. Here, we used cell- and subcompartment-specific proximity-dependent biotinylation3 to study the proteomes of striatal astrocytes and medium spiny neurons (MSNs) in vivo. We evaluated cytosolic and plasma membrane compartments for astrocytes and MSNs, revealing how these cells differ at the protein level and in their core signaling machinery. We assessed subcellular compartments of astrocytes including end feet and processes to reveal the molecular basis of essential astrocyte signaling and homeostatic functions. Unexpectedly, SAPAP3 proteins (gene; Dlgap3) associated with obsessive compulsive disorder (OCD) and repetitive behaviors4-11 were detected at equivalent levels in striatal astrocyte and MSN plasma membrane and cytosolic compartments. Astrocytic expression was confirmed by RNA-seq, fluorescence in situ hybridization and immunohistochemistry. Furthermore, genetic rescue experiments combined with behavioral analyses and proteomics in a mouse model4 of OCD lacking SAPAP3 revealed contributions of SAPAP3 in astrocytes and MSNs to repetitive and anxiety-related OCD behaviors. Our data define how astrocytes and neurons differ at the protein level and in their major signaling pathways, how astrocyte proteomes vary between physiological subcompartments, and how specific astrocyte and neuronal molecular mechanisms contribute to a psychiatric disease. Targeting both astrocytes and neurons together is likely to be therapeutically effective in complex CNS disorders.
HostingRepository	PRIDE
AnnounceDate	2023-01-13
AnnouncementXML	Submission_2023-01-13_13:40:27.479.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	YasamanJami-Alahmadi
SpeciesList	scientific name: Arabidopsis thaliana (Mouse-ear cress); NCBI TaxID: 3702; scientific name: Arachis hypogaea (Peanut); NCBI TaxID: 3818; scientific name: Brassica napus (Rape); NCBI TaxID: 3708; scientific name: Halobacterium salinarum; NCBI TaxID: 2242; scientific name: Candida albicans (Yeast); NCBI TaxID: 5476; scientific name: Acyrthosiphon pisum (Pea aphid); NCBI TaxID: 7029; scientific name: Equus caballus (Horse); NCBI TaxID: 9796; scientific name: Mesocricetus auratus (Golden hamster); NCBI TaxID: 10036; scientific name: Ictalurus punctatus (Channel catfish); NCBI TaxID: 7998; scientific name: Bombyx mori (Silk moth); NCBI TaxID: 7091; scientific name: Enterococcus faecalis (Streptococcus faecalis); NCBI TaxID: 1351; scientific name: Caenorhabditis elegans; NCBI TaxID: 6239; scientific name: Hepatitis C virus subtype 1a; NCBI TaxID: 31646; scientific name: Bos taurus (Bovine); NCBI TaxID: 9913; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Danio rerio (Zebrafish) (Brachydanio rerio); NCBI TaxID: 7955; scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227; scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Helicobacter pylori J99 (Campylobacter pylori J99); NCBI TaxID: 85963; scientific name: Merluccius bilinearis (Silver hake); NCBI TaxID: 79698; scientific name: Brassica oleracea var. botrytis (Cauliflower); NCBI TaxID: 3715; scientific name: Cicer arietinum (Chickpea) (Garbanzo); NCBI TaxID: 3827; scientific name: Cercopithecus aethiops (Green monkey) (Grivet); NCBI TaxID: 9534; scientific name: Heliocidaris erythrogramma (Sea urchin); NCBI TaxID: 7634; scientific name: Nicotiana tabacum (Common tobacco); NCBI TaxID: 4097; scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Apis mellifera (Honeybee); NCBI TaxID: 7460; scientific name: Macaca mulatta (Rhesus macaque); NCBI TaxID: 9544; scientific name: Dictyostelium discoideum (Slime mold); NCBI TaxID: 44689; scientific name: Gallus gallus (Chicken); NCBI TaxID: 9031; scientific name: Gadus morhua (Atlantic cod); NCBI TaxID: 8049; scientific name: Hordeum vulgare (Barley); NCBI TaxID: 4513;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-20 23:15:50	ID requested
⏵ 1	2023-01-13 13:40:27	announced

Dataset with its publication pending

submitter keyword: Astrocyte, LCMS, OCD

Dr. BaljitKhakh
contact affiliation	UCLA
contact email	bkhakh@mednet.ucla.edu
lab head
YasamanJami-Alahmadi
contact affiliation	UCLA
contact email	yjami@ucla.edu
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/2023/01/PXD029257

PRIDE project URI

• PRIDE
  1. PXD029257
     1. Label: PRIDE project
     2. Name: Astrocyte and neuron subcompartment proteomes reveal distinct cellular and molecular mechanisms of OCD