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Human Caspase-4 and -5 proteins have different expression profiles and biological functions

ABSTRACT: Inflammatory caspases are the central components of inflammasomes, among which the mouse Caspase-11 and human Caspase-4 and -5 are the core modules of non-canonical inflammasomes and function as the innate immune pattern recognition receptors (PRRs) for intracellular bacterial lipopolysaccharide (LPS). To answer the question why human encodes two proteins (Caspase-4 and -5) for this biological process instead of one (Caspase-11) in mouse, we examined the expression profiles and biological functions of human Caspase-4 and -5. In primary cultures of human monocyte-derived macrophages (MDMs) and colonic intestinal epithelial cell (IEC) organoids, we demonstrated that while Caspase-4 broadly expresses in different cell types, Caspase-5 is enriched in IECs and macrophages. To explore the biological roles of Caspase-5 in human IECs, we performed biotin proximity labeling assay to identify Caspase-5 associated proteins. Caspase-5a was fused with BioID2, a biotin ligase that indiscriminately biotinylate spatially close proteins, and expressed in human colonic organoids. Biotinylated proteins were then isolated and identified by protein mass spectrometry (MS). Intriguingly, all the three disheveled proteins in human (DVL1/2/3) were among the top identified targets (ranked by peptide-spectrum match (PSM)).

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Beatrix Ueberheide

PROVIDER: MSV000089179 | MassIVE | Thu Mar 31 09:50:00 BST 2022

REPOSITORIES: MassIVE

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