The evolution of the metazoan Toll receptor family and its expression during protostome development

Abstract Background Toll-like receptors (TLRs) play a crucial role in immunity and development. They contain leucine-rich repeat domains, one transmembrane domain, and one Toll/IL-1 receptor domain. TLRs have been classified into V-type/scc and P-type/mcc TLRs, based on differences in the leucine-rich repeat domain region. Although TLRs are widespread in animals, detailed phylogenetic studies of this gene family are lacking. Here we aim to uncover TLR evolution by conducting a survey and a phylogenetic analysis in species across Bilateria. To discriminate between their role in development and immunity we furthermore analyzed stage-specific transcriptomes of the ecdysozoans Priapulus caudatus and Hypsibius exemplaris, and the spiralians Crassostrea gigas and Terebratalia transversa. Results We detected a low number of TLRs in ecdysozoan species, and multiple independent radiations within the Spiralia. V-type/scc and P-type/mcc type-receptors are present in cnidarians, protostomes and deuterostomes, and therefore they emerged early in TLR evolution, followed by a loss in xenacoelomorphs. Our phylogenetic analysis shows that TLRs cluster into three major clades: clade α is present in cnidarians, ecdysozoans, and spiralians; clade β in deuterostomes, ecdysozoans, and spiralians; and clade γ is only found in spiralians. Our stage-specific transcriptome and in situ hybridization analyses show that TLRs are expressed during development in all species analyzed, which indicates a broad role of TLRs during animal development. Conclusions Our findings suggest that a clade α TLR gene (TLR-Ca) and a clade β/γ TLR gene (TLR-Cβ/γ) were already present in the cnidarian-bilaterian common ancestor. However, although TLR-Ca was conserved in cnidarians, TLR-Cβ/γ was lost during the early evolution of these taxa. Moreover, TLR-Cβ/γ duplicated to generate TLR-Cβ and TLR-Cγ in the lineage to the last common protostome-deuterostome ancestor. TLR-Ca, TLR-Cβ and TLR-Cγ further expanded generating the three major TLR clades. While all three clades radiated in several spiralian lineages, specific TLRs clades have been presumably lost in other lineages. Furthermore, the expression of the majority of these genes during protostome ontogeny suggests a likely role in development.

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The evolution of the metazoan Toll receptor family and its expression during protostome development

10.21203/rs.3.rs-199283/v1 ◽

2021 ◽

Author(s):

Andrea Orús-Alcalde ◽

Tsai-Ming Lu ◽

Andreas Hejnol

Keyword(s):

Phylogenetic Analysis ◽

Transmembrane Domain ◽

Leucine Rich Repeat ◽

Animal Development ◽

Phylogenetic Studies ◽

Repeat Domain ◽

Toll Receptor ◽

P Type

Abstract Background: Toll-like receptors (TLRs) play a crucial role in immunity and development. They contain leucine-rich repeat domains, one transmembrane domain, and one Toll/IL-1 receptor domain. TLRs have been classified into V-type/scc and P-type/mcc TLRs, based on differences in the leucine-rich repeat domain region. Although TLRs are widespread in animals, detailed phylogenetic studies of this gene family are lacking. Here we aim to uncover TLR evolution by conducting a survey and a phylogenetic analysis in species across Bilateria. To discriminate between their role in development and immunity we furthermore analyzed stage-specific transcriptomes of the ecdysozoans Priapulus caudatus and Hypsibius exemplaris, and the spiralians Crassostrea gigas and Terebratalia transversa.Results: We detected a low number of TLRs in ecdysozoan species, and multiple independent radiations within the Spiralia. V-type/scc and P-type/mcc type-receptors are present in cnidarians, protostomes and deuterostomes, and therefore they emerged early in TLR evolution, followed by a loss in xenacoelomorphs. Our phylogenetic analysis shows that TLRs cluster into three major clades: clade α is present in cnidarians, ecdysozoans, and spiralians; clade β in deuterostomes, ecdysozoans, and spiralians; and clade γ is only found in spiralians. Our stage-specific transcriptome and in situ hybridization analyses show that TLRs are expressed during development in all species analyzed, which indicates a broad role of TLRs during animal development.Conclusions: Our findings suggest that the bilaterian TLRs likely emerged by duplication from a single TLR encoding gene (proto-TLR) present in the last common cnidarian-bilaterian ancestor. This proto-TLR gene duplicated before the split of protostomes and deuterostomes; a second duplication occurred in the lineage to the Trochozoa. While all three clades further radiated in several spiralian lineages, specific TLRs clades have been presumably lost in others. Furthermore, the expression of the majority of these genes during protostome ontogeny suggests their involvement in immunity and development.

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The evolution of the metazoan Toll receptor family and its expression during protostome development

10.1101/2021.02.01.429095 ◽

2021 ◽

Author(s):

Andrea Orús-Alcalde ◽

Tsai-Ming Lu ◽

Andreas Hejnol

Keyword(s):

Phylogenetic Analysis ◽

Transmembrane Domain ◽

Leucine Rich Repeat ◽

Animal Development ◽

Phylogenetic Studies ◽

Repeat Domain ◽

Toll Receptor ◽

P Type

AbstractBackgroundToll-like receptors (TLRs) play a crucial role in immunity and development. They contain leucine-rich repeat domains, one transmembrane domain, and one Toll/IL-1 receptor domain. TLRs have been classified into V-type/scc and P-type/mcc TLRs, based on differences in the leucine-rich repeat domain region. Although TLRs are widespread in animals, detailed phylogenetic studies of this gene family are lacking. Here we aim to uncover TLR evolution by conducting a survey and a phylogenetic analysis in species across Bilateria. To discriminate between their role in development and immunity we furthermore analyzed stage-specific transcriptomes of the ecdysozoans Priapulus caudatus and Hypsibius exemplaris, and the spiralians Crassostrea gigas and Terebratalia transversa.ResultsWe detected a low number of TLRs in ecdysozoan species, and multiple independent radiations within the Spiralia. V-type/scc and P-type/mcc type-receptors are present in cnidarians, protostomes and deuterostomes, and therefore they emerged early in TLR evolution, followed by a loss in xenacoelomorphs. Our phylogenetic analysis shows that TLRs cluster into three major clades: clade α is present in cnidarians, ecdysozoans, and spiralians; clade β in deuterostomes, ecdysozoans, and spiralians; and clade γ is only found in spiralians. Our stage-specific transcriptome and in situ hybridization analyses show that TLRs are expressed during development in all species analyzed, which indicates a broad role of TLRs during animal development.ConclusionsOur findings suggest that the bilaterian TLRs likely emerged by duplication from a single TLR encoding gene (proto-TLR) present in the last common cnidarian-bilaterian ancestor. This proto-TLR gene duplicated before the split of protostomes and deuterostomes; a second duplication occurred in the lineage to the Trochozoa. While all three clades further radiated in several spiralian lineages, specific TLRs clades have been presumably lost in others. Furthermore, the expression of the majority of these genes during protostome ontogeny suggests their involvement in immunity and development.

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NF-κB-Inducing Kinase Regulates Selected Gene Expression in the Nod2 Signaling Pathway

Infection and Immunity ◽

10.1128/iai.74.4.2121-2127.2006 ◽

2006 ◽

Vol 74 (4) ◽

pp. 2121-2127 ◽

Cited By ~ 43

Author(s):

Qilin Pan ◽

Vladimir Kravchenko ◽

Alex Katz ◽

Shuang Huang ◽

Masayuki Ii ◽

...

Keyword(s):

Host Defense ◽

Innate Immune System ◽

Muramyl Dipeptide ◽

Innate Immune ◽

Host Responses ◽

Leucine Rich Repeat ◽

Wild Type ◽

Primary Explants ◽

Repeat Domain

ABSTRACT The innate immune system surveys the extra- and intracellular environment for the presence of microbes. Among the intracellular sensors is a protein known as Nod2, a cytosolic protein containing a leucine-rich repeat domain. Nod2 is believed to play a role in determining host responses to invasive bacteria. A key element in upregulating host defense involves activation of the NF-κB pathway. It has been suggested through indirect studies that NF-κB-inducing kinase, or NIK, may be involved in Nod2 signaling. Here we have used macrophages derived from primary explants of bone marrow from wild-type mice and mice that either bear a mutation in NIK, rendering it inactive, or are derived from NIK−/− mice, in which the NIK gene has been deleted. We show that NIK binds to Nod2 and mediates induction of specific changes induced by the specific Nod2 activator, muramyl dipeptide, and that the role of NIK occurs in settings where both the Nod2 and TLR4 pathways are activated by their respective agonists. Specifically, we have linked NIK to the induction of the B-cell chemoattractant known as BLC and suggest that this chemokine may play a role in processes initiated by Nod2 activation that lead to improved host defense.

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Differential expression of putative transbilayer amphipath transporters

Physiological Genomics ◽

10.1152/physiolgenomics.1999.1.3.139 ◽

1999 ◽

Vol 1 (3) ◽

pp. 139-150 ◽

Cited By ~ 52

Author(s):

MARGARET S. HALLECK ◽

JOSEPH F. LAWLER ◽

SETH BLACKSHAW ◽

LING GAO ◽

PRIYA NAGARAJAN ◽

...

Keyword(s):

Central Nervous System ◽

Phylogenetic Analysis ◽

Differential Expression ◽

Northern Analysis ◽

Gene Encoding ◽

Endocrine Organs ◽

Specific Manner ◽

The Central Nervous System ◽

P Type

Halleck, Margaret S., Joseph F. Lawler, Jr., Seth Blackshaw, Ling Gao, Priya Nagarajan, Coleen Hacker, Scott Pyle, Jason T. Newman, Yoshinobu Nakanishi, Hiroshi Ando, Daniel Weinstock, Patrick Williamson, and Robert A. Schlegel. Differential expression of putative transbilayer amphipath transporters. Physiol. Genomics 1: 139–150, 1999.—The aminophospholipid translocase transports phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Cloning of the gene encoding the enzyme identified a new subfamily of P-type ATPases, proposed to be amphipath transporters. As reported here, mammals express as many as 17 different genes from this subfamily. Phylogenetic analysis reveals the genes to be grouped into several distinct classes and subclasses. To gain information on the functions represented by these groups, Northern analysis and in situ hybridization were used to examine the pattern of expression of a panel of subfamily members in the mouse. The genes are differentially expressed in the respiratory, digestive, and urogenital systems, endocrine organs, the eye, teeth, and thymus. With one exception, all of the genes are highly expressed in the central nervous system (CNS); however, the pattern of expression within the CNS differs substantially from gene to gene. These results suggest that the genes are expressed in a tissue-specific manner, are not simply redundant, and may represent isoforms that transport a variety of different amphipaths.

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Role of Tropomodulin’s Leucine Rich Repeat Domain in the Formation of Neurite-like Processes

Biochemistry ◽

10.1021/bi401431k ◽

2014 ◽

Vol 53 (16) ◽

pp. 2689-2700 ◽

Cited By ~ 7

Author(s):

Laurent Guillaud ◽

Kevin T. Gray ◽

Natalia Moroz ◽

Caroline Pantazis ◽

Edward Pate ◽

...

Keyword(s):

Leucine Rich Repeat ◽

Leucine Rich Repeat Domain ◽

Repeat Domain

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Exosomes Regulate NLRP3 Inflammasome in Diseases

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.802509 ◽

2022 ◽

Vol 9 ◽

Author(s):

Zhangwang Li ◽

Xinyue Chen ◽

Junjie Tao ◽

Ao Shi ◽

Jing Zhang ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Critical Role ◽

Disease Process ◽

Diagnostic Tools ◽

Signal Molecules ◽

Leucine Rich Repeat ◽

Pyrin Domain ◽

Repeat Domain ◽

Oligomerization Domain

Emerging evidence has suggested the unique and critical role of exosomes as signal molecules vector in various diseases. Numerous researchers have been trying to identify how these exosomes function in immune progression, as this could promote their use as biomarkers for the disease process and potential promising diagnostic tools. NOD-like receptor (NLR) family, pyrin domain containing 3 (NLRP3), a tripartite protein, contains three functional domains a central nucleotide-binding and oligomerization domain (NACHT), an N-terminal pyrin domain (PYD), and a leucine-rich repeat domain (LRR). Of note, existing studies have identified exosome as a novel mediator of the NLRP3 inflammasome, which is critical in diseases progression. However, the actual mechanisms and clinical treatment related to exosomes and NLRP3 are still not fully understood. Herein, we presented an up-to-date review of exosomes and NLRP3 in diseases, outlining what is known about the role of exosomes in the activation of NLRP3 inflammasome and also highlighting areas of this topic that warrant further study.

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