Nlrp7

Okada K. 2004

NLRPs (acronym for "NIGHT, LRR and PYD domains-containing protein) are, together with the NOD1 and NOD2 proteins, members of the NLR (Nod-like Receptor) protein family and play a major role in innate immunity as pathogen recognition receptors (PPRs). Like the NOD proteins, NLRPs are expressed exclusively cytoplasmically. All NLRPs (they all contain a pyrin domain) are encoded by a common gene family in humans. NLRPs are characterised by their ability to activate different inflammatory complexes.

NLRP7 is a cytosolic protein encoded in humans by the NLRP7 gene located on chromosome 19q13.42 within a cluster of other NLRP genes. NLRP7 is, like NLRP1, NLRP2, NLRC4 and AIM-2, one of the NLRs that make up inflammasomes.

Inflammasomes are differently composed cytosolic protein complexes, whereby the different NLRPs are of great importance for their functionality. Inflammasomes are predominantly found in immune cells such as dendritic cells and macrophages.

The activation of an inflammasome complex leads to the expression of different caspases, which convert inactive interleukin-1beta and interleukin-18 into their active form.

NLRP7 (NALP7) can be detected in almost all tissues except heart, skeletal muscles and brain.

NLRP7 organizes itself, in response to various microbial lipopeptides and Staphylococcus infections, in a caspase-1-containing inflammatory complex (Radian AD et al. 2015)

NALP7 is a negative regulator of interleukin-1-beta, a cytokine that activates an immunological and inflammatory processes. Remarkably, IL1-beta is missing in the uterine environment during the periimplantation period.

Mahadevan et al (2014) demonstrate that NLRP7 can be detected in high concentrations in oocytes and early human embryos. In seminoma NLRP7 is upregulated.

There are numerous (also controversial) reports about mutations in the NLRP7 gene, which report about disturbances in embryonic development during pregnancy (formation of bladder moles) (Akoury E et al. 2015).

In studies by Slim et al (2012), a high frequency of NLRP7 polymorphism/mutations in Senegalese and Tunisian populations could be detected, which is associated with a higher frequency of bladder moles and chorionic carcinomas (in Northern Europe, the incidence of chorionic carcinoma is 1 in 2,000-3,000 births).

1. Abderrazak A et al (2015) NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol 4:296-307.
2. Akoury E et al. (2015) Live births in women with recurrent hydatidiform mole and two NLRP7 mutations. Reprod Biomed Online. 31:120-124.
3. Mahadevan S. et al (2014) NLRP7 affects trophoblast linear differentiation, binds to overexpressed YY1 and alters CpG methylation. Hum Molec Gene 23: 706-716.
4. Okada K et al (2004) Oncogenic role of NALP7 in testicular seminomas.Cancer Sci 95:949-954.
5. Radian AD et al (2015) ATP binding by NLRP7 is required for inflammasome activation in response to bacterial lipopeptides. Mol immunol 67:294-302.
6. Slim R et al (2012) NLRP7 and the genetics of post-molar choriocarcinomas in Senegal. Mol Hum Reprod 18:52-56.