Sialoadhesin

Sialoadhesin
Structure of the N-terminal domain of mouse sialoadhesin.[1]
Identifiers
SymbolSIGLEC1
Alt. symbolsSN, CD169
NCBI gene6614
HGNC11127
OMIM600751
PDB2BVE
RefSeqNM_023068
UniProtQ9BZZ2
Other data
LocusChr. 20 p13
Search for
StructuresSwiss-model
DomainsInterPro

Sialoadhesin (SIGLEC-1) is a cell adhesion molecule found on the surface of macrophages. It is found in especially high amounts on macrophages of the spleen, liver, lymph node, bone marrow, colon, and lungs.

Soluble SIGLEC-1 is a biomarker of monocyte-macrophage activation in systemic lupus erythematosus (SLE) and other autoimmune disorders.[2] In patients with rheumatoid arthritis, the protein has been found in great amounts on macrophages of the affected tissues.[3] It is defined as an I-type lectin, since it contains 17 immunoglobulin (Ig) domains (one variable domain and 16 constant domains), and thus also belongs to the immunoglobulin superfamily (IgSF). Sialoadhesin binds to certain molecules called sialic acids. During this binding process a salt bridge (protein) is formed between a highly conserved arginine residue (from the v-set domain to the 3'-sialyllactose) and the carboxylate group of the sialic acid.[3] Since sialoadhesin binds sialic acids with its N-terminal IgV-domain, it is also a member of the SIGLEC family. Alternate names for sialoadhesin include siglec-1 and CD169 (cluster of differentiation 169).[4]

Sialoadhesin predominantly binds neutrophils, but can also bind monocytes, natural killer cells, B cells and a subset of cytotoxic T cells by interacting with sialic acid molecules in the ligands on their surfaces.[5]

Sialoadhesin (CD169) positive macrophages, along with mesenchymal stem cells and beta-adrenergic neurons, form the hematopoietic stem cell niche in the bone marrow. CD169+ macrophages mediate signaling between the various cells and seem to promote hematopoietic stem cell retention to the niche. Siglec-1 is also expressed on lymph node subcapsular sinus macrophages. Research using a murine melanoma model has demonstrated that these subcapsular sinus macrophages bind to sialylated proteins present on the surface of pioneer metastatic cells shortly after their landing in the lymph nodes. This interaction serves as a critical step in metastatic colonization, providing a conducive environment, or 'soil,' for the establishment and proliferation of pioneer metastatic cells, often referred to as 'seeds.'[6]

  1. ^ PDB: 2BVE​; Zaccai NR, May AP, Robinson RC, Burtnick LD, Crocker PR, Brossmer R, Kelm S, Jones EY (February 2007). "Crystallographic and in silico analysis of the sialoside-binding characteristics of the Siglec sialoadhesin". J. Mol. Biol. 365 (5): 1469–79. doi:10.1016/j.jmb.2006.10.084. PMID 17137591.
  2. ^ Oliveira, João J.; Karrar, Sarah; Rainbow, Daniel B.; Pinder, Christopher L.; Clarke, Pamela; Rubio García, Arcadio; Al-Assar, Osama; Burling, Keith; Morris, Sian; Stratton, Richard; Vyse, Tim J.; Wicker, Linda S.; Todd, John A.; Ferreira, Ricardo C. (2018-07-27). "The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in systemic lupus erythematosus". Arthritis Research & Therapy. 20 (1): 152. doi:10.1186/s13075-018-1649-1. ISSN 1478-6362. PMC 6062988. PMID 30053827.
  3. ^ a b Hartnell A, Steel J, Turley H, Jones M, Jackson DG, Crocker PR (January 2001). "Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations". Blood. 97 (1): 288–96. doi:10.1182/blood.V97.1.288. PMID 11133773.
  4. ^ Varki A (2001-09-10). "Sialoadhesin, Siglec-1 (CD169)". Protein Reviews on the Web (PROW) Guide. United States National Center for Biotechnology Information (NCBI). Archived from the original on 2007-07-01. Retrieved 2011-04-15.
  5. ^ Kelm S, Pelz A, Schauer R, Filbin M, Tang S, de Bellard M, Schnaar R, Mahoney J, Hartnell A, Bradfield P (1994). "Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily". Curr Biol. 4 (11): 965–72. Bibcode:1994CBio....4..965K. doi:10.1016/S0960-9822(00)00220-7. PMID 7533044. S2CID 20282803.
  6. ^ Singh R, Choi BK (2019). "Siglec1-expressing subcapsular sinus macrophages provide soil for melanoma lymph node metastasis". eLife. 8: e48916. doi:10.7554/eLife.48916. PMC 6930078. PMID 31872800. S2CID 209461892.