29.6:
Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules, or Ig-CAMs, have a characteristic immunoglobulin protein fold in their multiple extracellular binding domains, called Ig-domains.
These Ig-domains allow the Ig-CAMs to function diversely across different tissue types.
For instance, neural or NCAMs expressed on neurons bind to each other via their Ig-domains to form homophilic interactions.
These interactions are involved in complex signaling pathways during neuronal differentiation and direct many contact-dependent processes, such as the growth of axons and dendrites.
In contrast, the Ig-domains of vascular or VCAMs, and intracellular or ICAMs, can bind different integrins — another type of cell adhesion molecule, thus exhibiting heterophilic interactions.
During an immune response, the vascular endothelium expresses these Ig-CAMs to recruit leukocytes from the bloodstream.
As the leukocytes slow down by selectin-mediated cell interactions, the integrins on their cell surface become activated.
This activation enables the integrins to firmly bind the Ig-CAMs on the endothelium and trigger various signaling cascades. The leukocyte finally passes between the endothelial cells to reach the destined tissue.
29.6:
Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs are involved in transient cell adhesion, the nectin class of molecules forms stable junctions, such as the adherens junctions, in conjunction with other CAMs. This versatility is reflected in diverse functions of Ig-CAMs, including cell adhesion and signaling, development, and infection.
Neural Ig-CAMS
Neurons express Ig-CAMs like NCAM and L1, which play an essential role in neural development. For example, children with L1 deficiency disease are missing two large nerve tracts, indicating the role of L1 in directing axon growth during embryonic development. Additionally, the homophilic interactions of NCAMs between neurons induce neurite outgrowth via the fibroblast growth factor receptor (FGFR). NCAMs continue to play a role in maintaining neural connections crucial for learning and forming memories.
Ig-CAMs in Disease
Ig-CAMs are involved in recruiting free-flowing leukocytes during an immune response. They play an important role in the extravasation of leukocytes from the bloodstream into the target tissue. Cancer cells hijack this process during metastasis to infiltrate a new site and form secondary tumors. Many cancers such as myeloid leukemia, pheochromocytoma, and Wilm’s tumor stain positive for NCAM2, and this property is used in pathology for tumor identification. Some Ig-CAMs also act as receptors for the entry of viruses into the host cell. Examples of viruses that utilize Ig-CAMs include the rabies virus and the human rhinovirus.
Suggested Reading
- Crossin, Kathryn L., and Leslie A. Krushel. "Cellular signaling by neural cell adhesion molecules of the immunoglobulin superfamily." Developmental dynamics: an official publication of the American Association of Anatomists 218.2 (2000): 260-279.