Proteomics

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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


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain, Cell Culture, Astrocyte

DISEASE(S): Spinal Cord Disease

SUBMITTER: Capuz Alice  

LAB HEAD: Michel Salzet

PROVIDER: PXD042754 | Pride | 2023-10-24

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
CTL-LPS-AC.txt Txt
IP-Pep.txt Txt
RAW-fig15-HeimIP.zip Other
Raw-fig12-ISOACCTL.zip Other
Raw-fig18-CRISPR.zip Other
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Publications

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.

Capuz Alice A   Osien Sylvain S   Cardon Tristan T   Karnoub Mélodie Anne MA   Aboulouard Soulaimane S   Raffo-Romero Antonella A   Duhamel Marie M   Cizkova Dasa D   Trerotola Marco M   Devos David D   Kobeissy Firas F   Vanden Abeele Fabien F   Bonnefond Amélie A   Fournier Isabelle I   Rodet Franck F   Salzet Michel M  

Cell death & disease 20230816 8


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 transcript. 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 tr  ...[more]

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