PXD061161-1

PXD061161 is an original dataset announced via ProteomeXchange.

Title	ATXN2L interacts mainly with NUFIP2, ATXN2L-absence causes NUFIP2 depletion, and ATXN2-polyQ expansion triggers NUFIP2 accumulation (Co-IPs)
Description	The cytoplasmic Ataxin-2 (ATXN2) protein associates with TDP-43 in stress granules (SG) where RNA quality control occurs. Mutations in this pathway underlie Spinocerebellar Ataxia type 2 (SCA2) and Amyotrophic Lateral Sclerosis. Ataxin-2-like (ATXN2L) is preferentially nuclear, more abundant, essential for embryonic life, and its sequestration into ATXN2 aggregates might contribute to disease. Here, two approaches elucidated ATXN2L roles. We identified (i) interactors by coimmunoprecipitation in wildtype and ATXN2L-null murine embryonic fibroblasts, (ii) proteome profile effects by mass spectrometry in these cells, (iii) ATXN2L interactor accumulation in the SCA2 mouse model Atxn2-CAG100-KnockIn (KIN). We observed RNA-binding proteins PABPN1, NUFIP2, MCRIP2, RBMS1, LARP1, PTBP1, FMR1, RPS20, FUBP3, MBNL2, ZMAT3, SFPQ, CSDE1, HNRNPK, and HNRNPDL to show mostly stronger association with ATXN2L than established interactors (ATXN2, PABPC1, LSM12, and G3BP2). ATXN2L also interacted with actin complex components SYNE2, LMOD1, ACTA2, FYB and GOLGA3. Oxidative stress increased HNRNPK but decreased SYNE2 association, likely reflecting SG relocalization. Among these interactors, proteome profiling revealed NUFIP2 and SYNE2 as depleted in ATXN2L-null fibroblasts. NUFIP2 homodimers and SYNE1 accumulated during the ATXN2 aggregation process in KIN 14-month-old spinal cords. Overall, the functions of ATXN2L and its interactors are important in RNA granule trafficking and surveillance, particularly for differentiated neuron maintenance
HostingRepository	PRIDE
AnnounceDate	2025-04-15
AnnouncementXML	Submission_2025-04-15_06:55:56.270.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: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-25 00:54:37	ID requested
⏵ 1	2025-04-15 06:55:56	announced

10.1016/J.NBD.2025.106903;

submitter keyword: ATXN2L

Georg Auburger
contact affiliation	Goethe University Frankfurt, University Hospital, Clinic of Neurology, Experimental Neurology, Heinrich Hoffmann Str. 7, 60590 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. PXD061161
     1. Label: PRIDE project
     2. Name: ATXN2L interacts mainly with NUFIP2, ATXN2L-absence causes NUFIP2 depletion, and ATXN2-polyQ expansion triggers NUFIP2 accumulation (Co-IPs)