TY - JOUR
T1 - Non-canonical roles of Siglecs: Beyond sialic acid-binding and immune cell modulation
AU - Siddiqui, Shoib
N1 - © 2022 Elsevier Ltd
PY - 2023/4/30
Y1 - 2023/4/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85137645023&partnerID=8YFLogxK
U2 - 10.1016/j.mam.2022.101145
DO - 10.1016/j.mam.2022.101145
M3 - Review article
SN - 0098-2997
VL - 90
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
M1 - 101145
ER -