NALP

NALP is a type of NOD-like receptor.[1] NALP proteins are part of the innate immunity and detect conserved pathogen characteristics such as peptidoglycan. It is thought that NALP proteins sense inherent danger, and link this with microbial products, creating a response under the concept of the inflammasome including K+ efflux and caspase 1 activation.[2] NALP is also known to be associated with a number of hereditary diseases. Research suggests NALP proteins may be involved in combating retroviruses in gametes.[3] Currently there are at least 13 known human NALP genes named as NALP1 through NALP13.[3]

Function

NALP plays a key role in inflammation and fevers. It is a scaffolding protein and is crucial for aggregating other proteins that form the inflammasome. It activates caspase-1 and assists in the maturation of the proinflammatory cytokines IL-1β and IL-18. As with other NOD-like receptors, NALP functions to recognize danger signals. NALP3 for instance has been observed to play a significant role propagating immune response to aluminum in adjuvants.[3][4][5][6]

Structure

NALP protein structure has a N-terminal PYD domain followed by NACHT domain and several leucine-rich repeats (LRR). These PYD domains can interact with other PYD domains to allow for interaction between NALP and other proteins also containing a PYD domain.[3][4][7]

Expression

NALP1 is highly expressed in neutrophils, monocytes, dendritic cells, B and T cells. NALP was found in high density in T-cell region of the spleen, but not found in B cell regions. Both the brain and the testis expressed NALP1 but not NALP3. NALP1 was found in the neurons of the brain.[4]

NALP gene

In humans, NALP genes are found on the following chromosomal localizations: 17p13, 19q13.42, 1q44, 19q13.43, 11p15.5, and 11p15.4. Most NALP genes are found on chromosome 19 and 11, however, the most abundant NALPs (NALP1 and NALP3) are found on 17p13 and 1q44. NALP has been frequently observed to undergo gene duplication events. [3][4]

Associated hereditary diseases

Mutations in the NALP3 is responsible for a number of hereditary diseases: MWS (Muckle-Wells Syndrome), FCAS (Familial Cold Autoinflammatory Syndrome) and CINCA (Chronic Infantile Neurological Cutaneous Articular syndrome). All of which involve periodic fever, joint inflammation, rashes and amyloidosis. Mutations in NALP genes that cause hereditary diseases is much more common than that of other PAMP receptors for unknown reasons. Experiments have suggested that Muckle-Wells syndrome is closely tied to IL-1 signaling, as when IL-1 receptor antagonists are introduced to patients, their inflammatory symptoms are no longer observed.[3][4][7]

Role in plants

In plants, danger signal sensors have been identified to contain many NALPs and therefore it is proposed that NALPs can also serve as danger signal sensors.[3]

References

  1. ↑ So, A (2008). "Developments in the scientific and clinical understanding of gout". Arthritis Research & Therapy. 10 (5): 221. doi:10.1186/ar2509.
  2. ↑ Martinon, F; Mayor, A; Tschopp, J (2009). "The inflammasomes: guardians of the body". Annu. Rev. Immunol. 27: 229–265. doi:10.1146/annurev.immunol.021908.132715.
  3. 1 2 3 4 5 6 7 Martinon, Fabio; Gaide, Olivier; Pétrilli, Virgine; Mayor, Annick; Tschopp, Jürg (2007-09-01). "NALP Inflammasomes: a central role in innate immunity". Seminars in Immunopathology. 29 (3): 213. doi:10.1007/s00281-007-0079-y. ISSN 1863-2297.
  4. 1 2 3 4 5 Kummer, Alain (May 2007). "Inflammasome Components NALP 1 and 3 Show Distinct but Separate Expression Profiles in Human Tissues Suggesting a Site-specific Role in the Inflammatory Response". Sage Journals.
  5. ↑ Kolliputi, Narasaiah; Galam, Lakshmi; Tamarapu Parthasarathy, Prasanna; Tipparaju, Srinivas M.; Lockey, Richard F. (2012-09-01). "NALP-3 inflammasome silencing attenuates ceramide-induced transepithelial permeability". Journal of Cellular Physiology. 227 (9): 3310–3316. doi:10.1002/jcp.24026. ISSN 1097-4652. PMC 3323724.
  6. ↑ Kolly, Laeticia; Karababa, Mahir; Joosten, Leo A. B.; Narayan, Sharmal; Salvi, Roberto; Pétrilli, Virginie; Tschopp, Jurg; Berg, Wim B. van den; So, Alexander Kai-Lik (2009-09-15). "Inflammatory Role of ASC in Antigen-Induced Arthritis Is Independent of Caspase-1, NALP-3, and IPAF". The Journal of Immunology. 183 (6): 4003–4012. doi:10.4049/jimmunol.0802173. ISSN 0022-1767. PMID 19717512.
  7. 1 2 "Unraveling the NALP-3/IL-1β Inflammasome: A Big Lesson from a Small Mutation". Immunity. 20 (3): 243–244. 2004-03-01. doi:10.1016/S1074-7613(04)00055-X. ISSN 1074-7613.
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