PXD042754

PXD042754 is an original dataset announced via ProteomeXchange.

Title	Heimdall, an alternative protein issued from a ncRNA related to kappa light chain variable region of immunoglobulins from astrocytes : a new player in neural proteome
Description	The dogma “One gene, one protein” is clearly obsolete since cells use alternative splicing and generate multiple transcripts which are translated into protein isoforms, but also use alternative translation initiation sites (TISs) and termination sites on a given transcripts. Alternative open reading frames for individual transcripts give proteins originate from the 5'- and 3'- UTR mRNA regions, frameshifts of mRNA ORFs or from non-coding RNAs. Longtime considered as non-coding, recent in-silico translation prediction methods enriched the protein databases allowing the identification of new target structures that have not been identified previously. To gain insight into the role of these newly identified alternative proteins in the regulation of cellular functions, it is crucial to assess their dynamic modulation within a framework of altered physiological modifications such as experimental spinal cord injury (SCI). Here, we carried out a longitudinal proteomic study on rat SCI from 12h to 10 days. Based on the alternative protein predictions, it was possible to identify a plethora of newly predicted protein hits. Among these proteins, some presented a special interest due to high homology with variable chain regions of immunoglobulins. We focus our interest on the one related to Kappa variable light chains which is similarly highly produced by B-cells in the Bence jones disease, but here expressed in astrocytes. This protein, name Heimdall is an Intrinsically disordered protein which is secreted under inflammatory conditions. Immunoprecipitation experiments showed that the Heimdall interactome contained proteins related to astrocyte fate keepers such as “NOTCH1, EPHA3, IPO13” as well as membrane receptor protein including “CHRNA9; TGFBR, EPHB6, and TRAM”. However, when Heimdall protein was neutralized utilizing a specific antibody or its gene knocked out by CRISPR-Cas9, sprouting elongations were observed in the corresponding astrocytes. Interestingly, depolarization assays and intracellular calcium measurements in Heimdall KO, established a depolarization effect on astrocyte membranes KO cells were more likely that the one found in neuroprogenitors. Proteomic analyses performed under injury conditions or under lipopolysaccharides (LPS) stimulation, revealed the expression of neuronal factors, stem cell proteins, proliferation, and neurogenesis of astrocyte convertor factors such as EPHA4, NOTCH2, SLIT3, SEMA3F, suggesting a role of Heimdall could regulate astrocytic fate. Taken together, Heimdall could be a novel member of the gatekeeping astrocyte-to-neuroprogenitor conversion factors.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:09:01.489.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Capuz Alice
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-06 03:03:13	ID requested
1	2023-10-24 11:30:27	announced
2	2023-11-14 09:07:44	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:09:02	announced	2024-10-22: Updated project metadata.

10.1038/s41419-023-06037-y;

Capuz A, Osien S, Cardon T, Karnoub MA, Aboulouard S, Raffo-Romero A, Duhamel M, Cizkova D, Trerotola M, Devos D, Kobeissy F, Vanden Abeele F, Bonnefond A, Fournier I, Rodet F, Salzet M, Heimdall, an alternative protein issued from a ncRNA related to kappa light chain variable region of immunoglobulins from astrocytes: a new player in neural proteome. Cell Death Dis, 14(8):526(2023) [pubmed]

ProteomeXchange project tag: Human Proteome Project

submitter keyword: Immunoglobulin,Astrocyte, Heimdall, Altprot

Michel Salzet
contact affiliation	Laboratoire PRISM INSERM U1192
contact email	michel.salzet@univ-lille.fr
lab head
Capuz Alice
contact affiliation	PRISM Laboratory
contact email	alice.capuz@univ-lille.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042754
     1. Label: PRIDE project
     2. Name: Heimdall, an alternative protein issued from a ncRNA related to kappa light chain variable region of immunoglobulins from astrocytes : a new player in neural proteome