Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva

Saitou, Marie; Gaylord, Eliza A.; Xu, Erica; May, Alison J.; Neznanova, Lubov; Nathan, Sara; Grawe, Anissa; Chang, Jolie L.; Ryan, William R.; Rühl, Stefan; Knox, Sarah M.; Gökçümen, Ömer

doi:10.1016/j.celrep.2020.108402

Cited by 69 publications

(77 citation statements)

References 117 publications

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“…CC-BY-NC-ND 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is The copyright holder for this preprint this version posted March 6, 2021. ; https://doi.org/10.1101/2021.03.05.433813 doi: bioRxiv preprint [27,28]. Lectin (carbohydrate-binding proteins), including conglutinin, SP-D, MBL, and SAP, bind selectively to specific carbohydrate structures (mannose-over galactosetype sugars) located at the head of the influenza HA of susceptible strains, thereby blocking the ability of HA to bind to sialylated cell-surface receptors [16,17].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is possible that sialic acid-independent factors are also involved in anti-IAV activity. One of the possible factors is the action of lectin-like proteins, such as ZG16B, which have shown a high correlation with anti-IAV activity [27,28]. Lectin (carbohydrate-binding proteins), including conglutinin, SP-D, MBL, and SAP, bind selectively to specific carbohydrate structures (mannose-over galactosetype sugars) located at the head of the influenza HA of susceptible strains, thereby blocking the ability of HA to bind to sialylated cell-surface receptors [16,17].…”

Section: Discussionmentioning

confidence: 99%

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Protein-bound sialic acid in saliva contributes directly to salivary anti-influenza virus activity

Kobayashi

Mori

et al. 2021

Preprint

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The oral cavity is an entrance for respiratory viruses, such as influenza. Recently, saliva has been shown to exert both antimicrobial and antiviral activities. Thus, saliva may be a biological factor that contributes to the prevention of influenza infection. However, the actual salivary anti-influenza A virus (IAV) activity in individuals and its determinant factors are unknown. By assessing individual variations in salivary anti-IAV activity in 92 people using an established new high-throughput system in this study, we found that the anti-IAV activity varied widely between individuals and showed a significant positive correlation with protein-bound sialic acid (BSA) level (ρ=0.473, p < 0.001). Furthermore, the anti-IAV activity of saliva with enzymatically reduced BSA content was significantly lower. These results indicate that BSA is a direct regulator of salivary anti-IAV activity and is a determinant of individual differences. Additionally, after comparing the anti-IAV activity across the groups by age, anti-IAV activity in young people (aged 5-19 years) were lower than in adults aged 20-59 years and elderly people aged 60-79 years. Our study suggests that BSA levels in saliva may be important in preventing influenza infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Protein-bound sialic acid in saliva contributes directly to salivary anti-influenza virus activity

Kobayashi

Mori

et al. 2021

Preprint

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“…Why venom isn't more common in mammals despite the high tissue specificity of venom homologs, or why venom homologs have less tissue specificity in some reptiles can be because of numerous factors. For example, perhaps selective pressures in mammals lead to an increase in regulatory complexity (for multifunctionality) in oral tissues rather than increasing dosage of a few (toxicopotent) components (Saitou et al 2020) . Or perhaps non-venomous reptiles occupied stable niches where evolution of a venom system wasn't required.…”

Section: Evolution Of Tetrapod Venoms By Kallikrein Exaptationmentioning

confidence: 99%

The parallel origins of vertebrate venoms

Barua

Koludarov

2021

Preprint

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Evolution can occur with surprising predictability when faced with similar ecological challenges. How and why this repeatability occurs remains a central question in evolutionary biology, but the complexity of most traits makes it challenging to answer. Reptiles and mammals independently evolved oral venoms that consist of proteinaceous cocktails which allow straightforward mapping between genotype and phenotype. Although biochemically similar toxins can occur as major venom components across many taxa, whether these toxins evolved via convergent or parallel means remains unknown. Most notable among them are kallikrein-like serine proteins, which form the core of most vertebrate venoms, and are employed by all venomous snake families. Here we used a combination of comparative genomics and phylogenetics to investigate whether serine protease recruitment into the venom occurred independently or in parallel across the different tetrapod lineages. Using syntenic relationships between genes flanking known toxins, we traced the origin of kallikreins to a single locus containing one or more nearby paralogous kallikrein-like clusters. Independently, phylogenetic analysis of vertebrate serine proteases revealed that the same gene cluster gave rise to toxins in mammals and reptiles. Given the shared regulatory and genetic machinery underlying venom evolution, these findings suggest a unified model underlying vertebrate venom evolution by exaptation of homologous ancestral kallikreins. Furthermore, the ubiquitous distribution of kallikreins across vertebrates suggests that the evolution of envenomation may be more common than previously recognized, blurring the line between venomous and non-venomous animals.

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“…Salivary proteins facilitate food perception and digestion, maintain the integrity of mineralized tooth and oral epithelial surfaces, shield the oral digestive tract from environmental hazards and invading pathogens, and protect oral tissues from fungal or viral infections [4,5]. Moreover, it is suggested that the origins of salivary proteins can be analyzed throughout mixed saliva and that post-transcriptional modifications may play a key role in understanding secretome network pathways [6,7]. Moreover, Feizi et al, 2020 [7] found that the study of secretion pathways (translocation, folding, trafficking and glycosylation) is relevant to know tissue-specific secretion pathways and tissuespecific secretomes that would facilitate the elaboration of a link between proteins and diseases.…”

Section: Introductionmentioning

confidence: 99%

The Salivary Secretome

Perpétuo¹,

Ferreira²,

Guedes³

et al. 2023

Periodontology - New Insights

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Recently, proteomics has emerged as an important tool for understanding biological systems, protein–protein interactions, and networks that ultimately lead to a deeper understanding of the underlying mechanisms of certain diseases. More recently, the study of secretomes, a type of proteomics, has also been highlighted as a potential next step in the field of diagnosis/prognosis. The secretome is the set of proteins expressed by an organism and secreted into the extracellular space, comprising 13–20% of all proteins. Since almost all, if not all, organs produce secretomes, this means that it is possible to study secretomes and trace these proteins back to their origin, supporting the idea that this could indeed be very important in diagnosing certain diseases. This is often combined with techniques such as mass spectrometry to measure the secretome of, for example, a particular tissue, and bioinformatics tools and databases to give us an idea of what to expect (prediction). In this paper, we will give a general overview of this world, but with a focus on the new bioinformatics tools and databases, their advantages and disadvantages, as well as a deeper look at isolation systems for proteomes, specifically salivary secretomes. Indeed, the salivary secretome represents a valuable new tool capable of providing insights into immunopathology and potentially aiding in diagnostics. Furthermore, we will explore applications of these methods and give an idea of what the future holds for such promising techniques: Salivary secretome in conjunction with bioinformatics tools/databases in the diagnosis of diseases (such as diabetes, Sjogren’s syndrome, and cardiovascular disease).

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Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva

Cited by 69 publications

References 117 publications

Protein-bound sialic acid in saliva contributes directly to salivary anti-influenza virus activity

Protein-bound sialic acid in saliva contributes directly to salivary anti-influenza virus activity

The parallel origins of vertebrate venoms

The Salivary Secretome

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