PXD064497-1

PXD064497 is an original dataset announced via ProteomeXchange.

Title	Conditional ATXN2L-nConditional ATXN2L-null in adult frontal cortex CamK2a+ neurons does not cause cell death, but restricts spontaneous mobility, and affects the alternative splicing pathway
Description	Ataxin-2-like (ATXN2L) protein is required to survive embryonic development, as documented in mice with constitutive absence of ATXN2L Lsm, LsmAD and PAM2 domains, due to knockout (KO) of exons 5-8 with frameshift. Its less abundant paralog Ataxin-2 (ATXN2) has an extended N-terminus, where a polyglutamine domain is prone to expansions, which mediate vulnerability to the polygenic adult motor neuron disease ALS (Amyotrophic Lateral Sclerosis), or cause the monogenic neurodegenerative processes of Spinocerebellar Ataxia type 2 (SCA2), depending on larger mutation sizes. Here, we elucidated the physiological function of ATXN2L by deleting the LsmAD and PAM2 motif, via loxP-mediated KO of exons 10-17 with frameshift. Crossing heterozygous floxed mice with constitutive Cre-deleter animals confirmed embryonic lethality among offspring. Crossing with CreERT2 mice and injecting tamoxifen for conditional deletion achieved (i) chimeric ATXN2L absence in half of CamK2a-positive frontal cortex neurons upon immunohistochemistry, with (ii) reductions of spontaneous horizontal movement. Global proteome profiling of frontal cortex homogenate found ATXN2L levels decreased to 75%, and dysregulations enriched in the alternative splicing pathway. Nuclear proteins with Sm domains are critical to perform splicing, so our data suggest that the Like-Sm (Lsm, LsmAD) domains in ATXN2L serve a role in splice regulation, despite its perinuclear location.
HostingRepository	PRIDE
AnnounceDate	2025-10-29
AnnouncementXML	Submission_2025-10-28_20:29:17.823.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Meierhofer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Ultra 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-01 23:34:31	ID requested
⏵ 1	2025-10-28 20:29:18	announced

Key J, Almaguer-Mederos LE, Kandi AR, Fellenz M, Gispert S, K, ö, pf G, Meierhofer D, Deller T, Auburger G, Conditional ATXN2L-Null in Adult Frontal Cortex CamK2a+ Neurons Does Not Cause Cell Death but Restricts Spontaneous Mobility and Affects the Alternative Splicing Pathway. Cells, 14(19):(2025) [pubmed]

10.3390/cells14191532;

submitter keyword: MRPL14, SRSF11, stress granules,Poly(A)-binding protein, NAA38, RPS3, label-free mass spectrometry, NSUN2, open field locomotion, ribonucleoproteins

Georg Auburger
contact affiliation	Goethe University Frankfurt, University Hospital, Clinic of Neurology, Experimental Neurology, Heinrich- Hoffmann-Str. 7, 60528 Frankfurt am Main, Germany
contact email	auburger@em.uni-frankfurt.de
lab head
David Meierhofer
contact affiliation	Mass Spectrometry Facility MPIMG
contact email	meierhof@molgen.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064497
     1. Label: PRIDE project
     2. Name: Conditional ATXN2L-nConditional ATXN2L-null in adult frontal cortex CamK2a+ neurons does not cause cell death, but restricts spontaneous mobility, and affects the alternative splicing pathway