NLRP: Difference between revisions
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'''NLRP''' or '''NALP''' is a type of [[NOD-like receptor]].<ref>{{cite journal | last1 = So | first1 = A | year = 2008 | title = Developments in the scientific and clinical understanding of gout | url = | journal = [[Arthritis Research & Therapy]] | volume = 10 | issue = 5| page = 221 | doi=10.1186/ar2509}}</ref> NLRP proteins are part of the innate immunity and detect conserved pathogen characteristics such as [[peptidoglycan]]. It is thought that NLRP proteins sense inherent danger, and link this with microbial products, creating a response under the concept of the [[inflammasome]] including [[Potassium|K]]<sup>+</sup> [[Flux (biology)|efflux]] and [[caspase 1]] activation.<ref>{{cite journal | last1 = Martinon | first1 = F | last2 = Mayor | first2 = A | last3 = Tschopp | first3 = J | year = 2009 | title = The inflammasomes: guardians of the body | url = | journal = Annu. Rev. Immunol. | volume = 27 | issue = | pages = 229–265 | doi=10.1146/annurev.immunol.021908.132715}}</ref> NLRP is also known to be associated with a number of hereditary diseases. Research suggests NLRP proteins may be involved in combating retroviruses in gametes.<ref name=":0">{{Cite journal|last=Martinon|first=Fabio|last2=Gaide|first2=Olivier|last3=Pétrilli|first3=Virgine|last4=Mayor|first4=Annick|last5=Tschopp|first5=Jürg|date=2007-09-01|title=NALP Inflammasomes: a central role in innate immunity|url=https://link.springer.com/article/10.1007/s00281-007-0079-y|journal=Seminars in Immunopathology|language=en|volume=29|issue=3|pages=213|doi=10.1007/s00281-007-0079-y|issn=1863-2297}}</ref> Currently there are at least 13 known human NALP genes named as NALP1 through NALP13.<ref name=":0" /> |
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== Function == |
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NLRP plays a key role in inflammation and fevers. It is a [[scaffold protein|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, NLRP functions to recognize danger signals. NALP3 for instance has been observed to play a significant role propagating immune response to aluminum in [[adjuvants]].<ref name=":0" /><ref name=":1">{{Cite journal|last=Kummer|first=Alain|date=May 2007|title=Inflammasome Components NALP 1 and 3 Show Distinct but Separate Expression Profiles in Human Tissues Suggesting a Site-specific Role in the Inflammatory Response|url=http://journals.sagepub.com/doi/abs/10.1369/jhc.6a7101.2006|journal=Sage Journals|volume=|pages=|via=}}</ref><ref>{{Cite journal|last=Kolliputi|first=Narasaiah|last2=Galam|first2=Lakshmi|last3=Tamarapu Parthasarathy|first3=Prasanna|last4=Tipparaju|first4=Srinivas M.|last5=Lockey|first5=Richard F.|date=2012-09-01|title=NALP-3 inflammasome silencing attenuates ceramide-induced transepithelial permeability|url=http://onlinelibrary.wiley.com/doi/10.1002/jcp.24026/abstract|journal=Journal of Cellular Physiology|language=en|volume=227|issue=9|pages=3310–3316|doi=10.1002/jcp.24026|issn=1097-4652|pmc=3323724}}</ref><ref>{{Cite journal|last=Kolly|first=Laeticia|last2=Karababa|first2=Mahir|last3=Joosten|first3=Leo A. B.|last4=Narayan|first4=Sharmal|last5=Salvi|first5=Roberto|last6=Pétrilli|first6=Virginie|last7=Tschopp|first7=Jurg|last8=Berg|first8=Wim B. van den|last9=So|first9=Alexander Kai-Lik|date=2009-09-15|title=Inflammatory Role of ASC in Antigen-Induced Arthritis Is Independent of Caspase-1, NALP-3, and IPAF|url=http://www.jimmunol.org/content/183/6/4003|journal=The Journal of Immunology|language=en|volume=183|issue=6|pages=4003–4012|doi=10.4049/jimmunol.0802173|issn=0022-1767|pmid=19717512}}</ref> |
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== Structure == |
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NLRP protein structure has a N-terminal [[Pyrin domain|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 NRLP and other proteins also containing a PYD domain.<ref name=":0" /><ref name=":1" /><ref name=":2">{{Cite journal|date=2004-03-01|title=Unraveling the NALP-3/IL-1β Inflammasome: A Big Lesson from a Small Mutation|url=https://www.sciencedirect.com/science/article/pii/S107476130400055X|journal=Immunity|language=en|volume=20|issue=3|pages=243–244|doi=10.1016/S1074-7613(04)00055-X|issn=1074-7613}}</ref> |
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== Expression == |
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NLRP1 is highly expressed in [[neutrophils]], [[monocytes]], [[dendritic cells]], B and T cells. NLRP 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 NLRP1 but not NLRP3. NLRP1 was found in the neurons of the brain.<ref name=":1" /> |
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== NALP gene == |
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In humans, NRLP genes are found on the following chromosomal localizations: 17p13, 19q13.42, 1q44, 19q13.43, 11p15.5, and 11p15.4. Most NRLP genes are found on chromosome 19 and 11, however, the most abundant NLRPs (NLRP1 and NLRP3) are found on 17p13 and 1q44. NLRP has been frequently observed to undergo [[gene duplication]] events.<ref name=":0" /><ref name=":1" /> |
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== Associated hereditary diseases == |
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Mutations in the NLRP3 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 NLRP 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.<ref name=":0" /><ref name=":1" /><ref name=":2" /> |
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== Role in plants == |
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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.<ref name=":0" /> |
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== Genes == |
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* [[NLRP1]], a human gene that encodes the NACHT, LRR and PYD domains-containing protein 1 |
* [[NLRP1]], a human gene that encodes the NACHT, LRR and PYD domains-containing protein 1 |
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* [[NLRP2]], a human gene that encodes the NACHT, LRR and PYD domains-containing protein 2 |
* [[NLRP2]], a human gene that encodes the NACHT, LRR and PYD domains-containing protein 2 |
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* [[NLRP12]], a human gene that encodes the NACHT, LRR and PYD domains-containing protein 12 |
* [[NLRP12]], a human gene that encodes the NACHT, LRR and PYD domains-containing protein 12 |
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Some NLRP genes encode a series of [[NOD-like receptor]] family pyrin domains, including: |
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* [[NLRP5]], a human gene that encodes the NOD-like receptor family pyrin domain containing 5 |
* [[NLRP5]], a human gene that encodes the NOD-like receptor family pyrin domain containing 5 |
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* [[NLRP6]], a human gene that encodes the NOD-like receptor family pyrin domain containing 6 |
* [[NLRP6]], a human gene that encodes the NOD-like receptor family pyrin domain containing 6 |
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* [[NLRP14]], a human gene that encodes the NOD-like receptor family pyrin domain containing 14 |
* [[NLRP14]], a human gene that encodes the NOD-like receptor family pyrin domain containing 14 |
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== References == |
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{{dab}} |
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{{reflist}} |
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[[Category:Intracellular receptors]] |
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Revision as of 19:51, 5 November 2018
NLRP or NALP is a type of NOD-like receptor.[1] NLRP proteins are part of the innate immunity and detect conserved pathogen characteristics such as peptidoglycan. It is thought that NLRP 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] NLRP is also known to be associated with a number of hereditary diseases. Research suggests NLRP 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
NLRP 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, NLRP 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
NLRP 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 NRLP and other proteins also containing a PYD domain.[3][4][7]
Expression
NLRP1 is highly expressed in neutrophils, monocytes, dendritic cells, B and T cells. NLRP 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 NLRP1 but not NLRP3. NLRP1 was found in the neurons of the brain.[4]
NALP gene
In humans, NRLP genes are found on the following chromosomal localizations: 17p13, 19q13.42, 1q44, 19q13.43, 11p15.5, and 11p15.4. Most NRLP genes are found on chromosome 19 and 11, however, the most abundant NLRPs (NLRP1 and NLRP3) are found on 17p13 and 1q44. NLRP has been frequently observed to undergo gene duplication events.[3][4]
Associated hereditary diseases
Mutations in the NLRP3 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 NLRP 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]
Genes
Some NLRP genes code for a series of NACHT, LRR and PYD domains-containing proteins, including:
- NLRP1, a human gene that encodes the NACHT, LRR and PYD domains-containing protein 1
- NLRP2, a human gene that encodes the NACHT, LRR and PYD domains-containing protein 2
- NLRP3, a human gene that encodes the NACHT, LRR and PYD domains-containing protein 3
- NLRP4, a human gene that encodes the NACHT, LRR and PYD domains-containing protein 4
- NLRP7, a human gene that encodes the NACHT, LRR and PYD domains-containing protein 7
- NLRP12, a human gene that encodes the NACHT, LRR and PYD domains-containing protein 12
Some NLRP genes encode a series of NOD-like receptor family pyrin domains, including:
- NLRP5, a human gene that encodes the NOD-like receptor family pyrin domain containing 5
- NLRP6, a human gene that encodes the NOD-like receptor family pyrin domain containing 6
- NLRP8, a human gene that encodes the NOD-like receptor family pyrin domain containing 8
- NLRP9, a human gene that encodes the NOD-like receptor family pyrin domain containing 9
- NLRP10, a human gene that encodes the NOD-like receptor family pyrin domain containing 10
- NLRP11, a human gene that encodes the NOD-like receptor family pyrin domain containing 11
- NLRP13, a human gene that encodes the NOD-like receptor family pyrin domain containing 13
- NLRP14, a human gene that encodes the NOD-like receptor family pyrin domain containing 14
References
- ^ So, A (2008). "Developments in the scientific and clinical understanding of gout". Arthritis Research & Therapy. 10 (5): 221. doi:10.1186/ar2509.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ 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.
- ^ a b c d e f g 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.
- ^ a b c d e 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.
- ^ 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.
- ^ 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.
- ^ a b "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.