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http://purl.uniprot.org/citations/37944639http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37944639http://www.w3.org/2000/01/rdf-schema#comment"

Aims

TAFA2, a cytokine specifically expressed in the central nervous system, plays a vital role in neuronal cell survival. TAFA2 deficiency has been correlated to various neurological disorders in mice and humans. However, the underlying mechanism remains elusive, especially its membrane-binding receptor through which TAFA2 functions. This study aimed to identify the specific binding receptor responsible for the anti-apoptotic effects of TAFA2.

Main method

Co-immunoprecipitation (Co-IP) and quantitative mass spectrometry-based proteomic analysis were employed to identify potential TAFA2 binding proteins in V5 knockin mouse brain lysates. Subsequent validation involved in vitro and in vivo Co-IP and pull-down using specific antibodies. The functional analysis included evaluating the effects of ADGRL1 knockout, overexpression, and Lectin-like domain (Lec) deletion mutant on TAFA2's anti-apoptotic activity and analyzing the intracellular signaling pathways mediated by TAFA2 through ADGRL1.

Key findings

Our study identified ADGRL1 as a potential receptor for TAFA2, which directly binds to TAFA2 through its lectin-like domain. Overexpression ADGRL1, but not ADGRL1ΔLec, induced apoptosis, which could be effectively suppressed by recombinant TAFA2 (rTAFA2). In ADGRL1-/- cells or re-introducing with ADGRL1ΔLec, responses to rTAFA2 in suppressing cell apoptosis were compromised. Increased cAMP, p-PKA, p-CREB, and BCL2 levels were also observed in response to rTAFA2 treatment, with these responses attenuated in ADGRL1-/- or ADGRL1ΔLec-expressing cells.

Significance

Our results demonstrated that TAFA2 directly binds to the lectin-like domain of ADGRL1, activating cAMP/PKA/CREB/BCL2 signaling pathway, which is crucial in preventing cell death. These results implicate TAFA2 and its receptor ADGRL1 as potential therapeutic targets for neurological disorders."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.org/dc/terms/identifier"doi:10.1016/j.lfs.2023.122241"xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/author"Liang H."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/author"Shen Y."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/author"Chen M.M."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/author"Shen C.L."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/author"Fei J."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/author"Lu S.Y."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/author"Wang Z.G."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/author"Zhang H.X."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/author"Ge H.Y."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/author"Tang L.Y."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/name"Life Sci"xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/pages"122241"xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/title"Neuronal survival factor TAFA2 suppresses apoptosis through binding to ADGRL1 and activating cAMP/PKA/CREB/BCL2 signaling pathway."xsd:string
http://purl.uniprot.org/citations/37944639http://purl.uniprot.org/core/volume"334"xsd:string
http://purl.uniprot.org/citations/37944639http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/37944639
http://purl.uniprot.org/citations/37944639http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/37944639
http://purl.uniprot.org/uniprot/#_A0A0R4J0M7-mappedCitation-37944639http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37944639
http://purl.uniprot.org/uniprot/#_P10417-mappedCitation-37944639http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37944639
http://purl.uniprot.org/uniprot/#_Q62347-mappedCitation-37944639http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37944639
http://purl.uniprot.org/uniprot/#_Q61440-mappedCitation-37944639http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37944639
http://purl.uniprot.org/uniprot/#_Q61441-mappedCitation-37944639http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37944639
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