SLURP1, secreted Ly6/Plaur domain containing 1, is a secreted member of the LY6/PLAUR protein family. It serves as an endogenous ligand for the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) and is involved in multiple biological processes. Mutations in the SLURP1 gene are associated with Mal de Meleda, a rare autosomal recessive genetic disease characterized by inflammatory palmoplantar keratoderma [2].

In E. coli K1 meningitis, an infection in neonates, E. coli K1 infection triggers the release of SLURP1. Exogenous supplement, knockdown, or overexpression experiments show that SLURP1 is required for E. coli K1 invasion and neutrophils migrating across the blood-brain barrier (BBB). Its promoting effect on the pathogenesis of E. coli K1 meningitis is abolished in α7 nAChR knockout mice, indicating that E. coli K1 exploits SLURP1 to activate α7 nAChR and facilitate its pathogenesis [1]. In SLURP1 and SLURP2 knockout mouse models of hereditary palmoplantar keratoderma, both models exhibit hypersensitivity to mechanical and thermal stimuli as well as spontaneous pain behaviors, suggesting an association between SLURP1 deficiency and pain hypersensitivity [3].

In summary, SLURP1 is crucial in processes related to E. coli K1 meningitis pathogenesis and pain sensitivity in palmoplantar keratoderma. Gene knockout mouse models have been instrumental in revealing these functions, highlighting its potential as a therapeutic target for related diseases.

References:

1. He, Xiaolong, Wang, Lei, Liu, Liqun, Cao, Hong, Huang, Sheng-He. 2021. Endogenous α7 nAChR Agonist SLURP1 Facilitates Escherichia coli K1 Crossing the Blood-Brain Barrier. In Frontiers in immunology, 12, 745854. doi:10.3389/fimmu.2021.745854. https://pubmed.ncbi.nlm.nih.gov/34721415/

2. Favre, Bertrand, Plantard, Laure, Aeschbach, Lorène, Huber, Marcel, Hohl, Daniel. 2006. SLURP1 is a late marker of epidermal differentiation and is absent in Mal de Meleda. In The Journal of investigative dermatology, 127, 301-8. doi:. https://pubmed.ncbi.nlm.nih.gov/17008884/

3. Weinberg, Rachel L, Kim, Suyeon, Pang, Zixuan, Qu, Lintao, Caterina, Michael J. 2024. Pain Hypersensitivity in SLURP1 and SLURP2 Knock-out Mouse Models of Hereditary Palmoplantar Keratoderma. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 44, . doi:10.1523/JNEUROSCI.0260-23.2024. https://pubmed.ncbi.nlm.nih.gov/38866482/