ICAM3

ICAM3 is a 110–160 kDa protein that belongs to the intercellular adhesion molecule (ICAM) family. Like the other proteins in this family, ICAM3 is a type I transmembrane glycoprotein and consists in part of a hydrophobic transmembrane domain and a short domain that extends into the cytoplasm.{{cite journal | vauthors = Smith CW | title = 3. Adhesion molecules and receptors | journal = The Journal of Allergy and Clinical Immunology | volume = 121 | issue = 2 Suppl | pages = S375-9; quiz S414 | date = February 2008 | pmid = 18241685 | doi = 10.1016/j.jaci.2007.07.030 | series = 2008 Mini-Primer on Allergic and Immunologic Diseases | doi-access = free }} ICAM3 also contains five extracellular immunoglobulin domains.

ICAM3 is found on the surface of leukocytes, and the ICAM3 gene is constitutively expressed in these cells. Interactions between ICAM3 and specific integrin receptors facilitate adhesion between cells.

ICAM3 has an important function in the immune cell response, as it helps facilitate initial interactions between T cells and dendritic cells.{{cite journal | vauthors = van Kooyk Y, Geijtenbeek TB | title = A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions | journal = Immunological Reviews | volume = 186 | pages = 47–56 | date = August 2002 | pmid = 12234361 | doi = 10.1034/j.1600-065x.2002.18605.x | s2cid = 23267228 }} Resting T cells show high levels of ICAM3 expression. ICAM3 on these T cells can bind to DC-SIGN, a transmembrane receptor present on dendritic cells, creating temporary contact between resting T cells and dendritic cells. This adhesion allows the T cell receptor (TCR) to interact with major histocompatibility complex (MHC) molecules on the surface of the dendritic cell, which, upon binding between the TCR, the MHC, and the peptide coupled to the MHC, facilitates T cell activation.

ICAM3 plays a role in apoptotic cell clearance by promoting the movement of macrophages, which ingest and break down unhealthy cells via phagocytosis, to cells undergoing apoptosis. Apoptotic cells can release extracellular vesicles containing ICAM3, which acts as a chemoattractant to phagocytes such as macrophages, directing them toward apoptotic cells.{{cite journal | vauthors = Hawkins LA, Devitt A | title = Current understanding of the mechanisms for clearance of apoptotic cells-a fine balance | journal = Journal of Cell Death | volume = 6 | pages = 57–68 | date = January 2013 | pmid = 25278779 | pmc = 4147779 | doi = 10.4137/jcd.s11037 }} Apoptotic cells also contain altered ICAM3 proteins on their surface. These altered proteins allow macrophages to specifically target and bind apoptotic cells. This process is believed to involve binding between ICAM3 and CD14 receptors, which are a type of cell surface receptor expressed on macrophages and other phagocytes.

ICAM3 is also found on mast cells, another type of leukocyte. Mast cells taken from human lungs and the HMC-1 line, a human mast cell line, both showed expression of ICAM3. ICAM3 helps mediate the adhesion of mast cells to the extracellular matrix.

Binding between ICAM3 and DC-SIGN, which takes place during initial interactions between T cells and dendritic cells, occurs with high affinity.{{cite journal | vauthors = Rahimi N | title = C-type Lectin CD209L/L-SIGN and CD209/DC-SIGN: Cell Adhesion Molecules Turned to Pathogen Recognition Receptors | journal = Biology | volume = 10 | issue = 1 | pages = 1 | date = December 2020 | pmid = 33375175 | pmc = 7822156 | doi = 10.3390/biology10010001 | doi-access = free }} This binding process is also calcium-dependent.

CD14, a receptor expressed on the surface of phagocytes, can also bind ICAM3. Interactions between CD14 and altered ICAM3 molecules on apoptotic cells are believed to help promote phagocytosis of apoptotic cells.

ICAM3 is a known ligand for LFA-1, an integrin expressed by leukocytes. To facilitate binding, the I domain of LFA-1 interacts with the ICAM3 protein’s first immunoglobulin domain. ICAM3 also binds the integrin αDβ2.

ICAM3 has been shown to interact with activated ERM proteins, including ezrin (EZR) and moesin, in T cells.{{cite book | vauthors = Cornely R, Grewal T, Gaus K | chapter = The Actin Cytoskeleton and Membrane Organisation in T Lymphocytes |date=2012 | title = Cytoskeleton and Human Disease |pages=103–121 | veditors = Kavallaris M |place=Totowa, NJ |publisher=Humana Press |language=en |doi=10.1007/978-1-61779-788-0_5 |isbn=978-1-61779-788-0 }}

• Cluster of differentiation

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• {{cite journal | vauthors = Bernstein CN, Sargent M, Gallatin WM | title = Beta2 integrin/ICAM expression in Crohn's disease | journal = Clinical Immunology and Immunopathology | volume = 86 | issue = 2 | pages = 147–160 | date = February 1998 | pmid = 9473377 | doi = 10.1006/clin.1997.4462 }}

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• {{MeshName|ICAM3+protein,+human}}

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Category:Clusters of differentiation