{"title":"Non-canonical roles of Siglecs: Beyond sialic acid-binding and immune cell modulation","authors":"Shoib Sarwar Siddiqui","doi":"10.1016/j.mam.2022.101145","DOIUrl":null,"url":null,"abstract":"<div><p>Siglecs (Sialic acid-binding immunoglobulin-type lectins) are I-type lectins that bind with sialic acid ligands (Sia). Most are expressed on the surface of leukocytes and are involved in immune regulation and possess immune tyrosine-based inhibitory motif (ITIM) in the intracellular domain, thus leading to inhibition of the immune response. This signaling is instrumental in maintaining quiescence under physiological conditions and acts as a brake for inflammatory cascades. By contrast, activating Siglecs carry positively charged residues in the transmembrane domain and interact with immune tyrosine-based activating motif (ITAM)-containing proteins, a DNAX-activating protein of 10–12 kDa (DAP10/12), to activate immune cells. There are various characteristics of Siglecs that do not fit within the classification of Siglec receptors as being either inhibitory or activating in nature. This review focuses on elucidating the non-canonical functions and interactions of Siglec receptors, which include Sia-independent interactions such as protein-protein interactions and interactions with lipids or other sugars. This review also summarizes Siglec expression and function on non-immune cells, and non-classical signaling of the receptor. Thus, this review will be beneficial to researchers interested in the field of Siglecs and sialic acid biology.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":8.7000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Aspects of Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0098299722000905","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 4
Abstract
Siglecs (Sialic acid-binding immunoglobulin-type lectins) are I-type lectins that bind with sialic acid ligands (Sia). Most are expressed on the surface of leukocytes and are involved in immune regulation and possess immune tyrosine-based inhibitory motif (ITIM) in the intracellular domain, thus leading to inhibition of the immune response. This signaling is instrumental in maintaining quiescence under physiological conditions and acts as a brake for inflammatory cascades. By contrast, activating Siglecs carry positively charged residues in the transmembrane domain and interact with immune tyrosine-based activating motif (ITAM)-containing proteins, a DNAX-activating protein of 10–12 kDa (DAP10/12), to activate immune cells. There are various characteristics of Siglecs that do not fit within the classification of Siglec receptors as being either inhibitory or activating in nature. This review focuses on elucidating the non-canonical functions and interactions of Siglec receptors, which include Sia-independent interactions such as protein-protein interactions and interactions with lipids or other sugars. This review also summarizes Siglec expression and function on non-immune cells, and non-classical signaling of the receptor. Thus, this review will be beneficial to researchers interested in the field of Siglecs and sialic acid biology.
期刊介绍:
Molecular Aspects of Medicine is a review journal that serves as an official publication of the International Union of Biochemistry and Molecular Biology. It caters to physicians and biomedical scientists and aims to bridge the gap between these two fields. The journal encourages practicing clinical scientists to contribute by providing extended reviews on the molecular aspects of a specific medical field. These articles are written in a way that appeals to both doctors who may struggle with basic science and basic scientists who may have limited awareness of clinical practice issues. The journal covers a wide range of medical topics to showcase the molecular insights gained from basic science and highlight the challenging problems that medicine presents to the scientific community.