There are four major superfamilies or groups of CAMs: the
immunoglobulin superfamily (
IgSF CAMs),
cadherins,
integrins, and the superfamily of
C-type of lectin-like domains proteins (CTLDs).
Proteoglycans are also considered to be a class of CAMs. One classification system involves the distinction between calcium-independent CAMs and calcium-dependent CAMs. The Ig-superfamily CAMs do not depend on Ca2+ while integrins, cadherins and selectins depend on Ca2+. In addition, integrins participate in cell–matrix interactions, while other CAM families participate in cell–cell interactions.
Calcium-independent Immunoglobulin superfamily CAMs (
IgSF CAMs) is regarded as the most diverse superfamily of CAMs. This family is characterized by their extracellular domains containing Ig-like domains. The Ig domains are then followed by
fibronectin type III domain repeats and IgSFs are anchored to the membrane by a GPI moiety. This family is involved in both homophilic or heterophilic binding and has the ability to bind integrins or different IgSF CAMs.
Calcium-dependent Integrins, one of the major classes of receptors within the ECM, mediate cell–ECM interactions with
collagen,
fibrinogen,
fibronectin, and
vitronectin. Integrins provide essential links between the
extracellular environment and the intracellular signalling pathways, which can play roles in cell behaviours such as
apoptosis,
differentiation,
survival, and
transcription. Integrins are
heterodimeric, as they consist of an alpha and beta subunit. There are currently 18 alpha subunits and 8 beta subunits, which combine to make up 24 different integrin combinations. The extracellular domain is where the
ligand binds through the use of divalent
cations. The integrins contain multiple divalent cation binding sites in the extracellular domain ). The integrin cation binding sites can be occupied by Ca2+ or by Mn2+ ions. Cations are necessary but not sufficient for integrins to convert from the inactive bent conformation into the active extended conformation. Both the presence of cations bound to the multiple cation binding sites is required, along with the direct physical association with ECM ligands for integrins to attain the extended structure and concomitant activation. Thus, rise in extracellular Ca2+ ions may serve to prime the integrin heterodimer. The release of intracellular Ca2+ have been shown to be important for integrin inside-out activation. However, extracellular Ca2+ binding may exert different effects depending on the type of integrin and the cation concentration. Integrins regulate their activity within the body by changing conformation. Most exist at rest in a low
affinity state, which can be altered to high affinity through an external agonist which causes a conformational change within the integrin, increasing their affinity. The classic cadherins (
E-,
N- and
P-) are concentrated at the
intermediate cell junctions, which link to the
actin filament network through specific linking proteins called
catenins.
Selectins Selectins are a family of heterophilic CAMs that are dependent on
fucosylated carbohydrates, such as
mucins for binding. The three family members are
E-selectin (
endothelial),
L-selectin (
leukocyte), and
P-selectin (
platelet). The best-characterized ligand for the three selectins is
P-selectin glycoprotein ligand-1 (PSGL-1), which is a mucin-type glycoprotein expressed on all white blood cells. Selectins have been implicated in several roles but they are especially important in the immune system by helping white blood cell homing and trafficking. ==Function==