Cell adhesion molecules
What are cell adhesion molecules?
Cell adhesion molecules or CAMs are specialised cell-surface glycoproteins that aid in a number of cellular processes such as:
These molecules can be classified into four major families: selectins, integrins, cadherins, and the Ig superfamily.
Selectins are a family of carbohydrate-binding glycoproteins expressed on leukocytes and endothelial cells. There are three classes of selectins: endothelial (E)-selectin, leukocyte (L)-selectin, and platelet (P)-selectin.
These three types of selectins share similar structure, with each having: (a) a calcium-dependent lectin domain on the N-terminus, (b) an epidermal growth factor (EGF) domain (c) and a number of varied repeat units. Surprisingly, the transmembrane domain and the intracellular cytoplasmic tail are not conserved among the selectin classes. The two structures are important for the targeting of compartments (Figure 1).
The function of selectins is important as they are involved in lymphocyte homing, inflammation and immune responses.
Integrins serve as receptor proteins which mediate the interactions between other cells and the extracellular matrix. The integrins are heavily involved in cell communication, motility and regulation of the cell cycle.
The integrins are heterodimers which are composed of two chains called alpha and beta subunits as shown in Figure 2. These subunits span across the plasma membrane. Each alpha and beta subunit contains two separate tails which allow the integrin penetrate the plasma membrane. A number of alpha and beta subunits exist and are characterised according to their structure.
Cadherins are important transmembrane proteins that are found in the tissues of both invertebrates and vertebrates. Their main function involves the development, structure and organization of embryonic tissue. There are multiple classes of cadherins which can be found in various tissues and include the classical and non-classical families.
The classical family includes placental (P)-cadherin, neural (N)-cadherin and epithelial (E)-cadherin which were the first to be identified. The classical cadherin structure is composed of five extraceullar (EC) domains (numbered 1-5 start at the N-terminus) that serve as binding sites for Ca+ ions. These EC domains are followed by a transmembrane domain region, and cytoplasmic domain (Figure 3).
The other two classes include non-classical cadherins such as the desmosomal cadherins (comprised of desmogleins and desmocollin) and proto-cadherins.
One unique feature of this class of these adhesive molecules is their dependence on calcium to function. The cadherin structure contains a number of repeats which are capable of binding to Ca2+. Once bound to calcium, the cadherin becomes rigid in structure facilitating the tissue structure.
The Ig superfamily is composed of a number of molecules which include co-receptors (CD-4), antigenic receptors (T-cell Receptor) antigenic presenting molecules (MHC Class I) and immune system stimulators.The role of the Ig superfamily is primarily related to the immune system.
This class of family share a similar structure with a common domain termed the immunoglobulin domain. This domain is comprised of up to 110 amino acids and has a characteristic fold which is formed by two beta sheets that are anti-parallel. Structurally, this Ig superfamily also share some type of domain variable or constant with disulfide bonds (s-s) followed by a transmembrane portion. (Figure 4)
Addtional reading and articles:
Gonzalez-Amaro, R. & F. Sanchez-Madrid (1999) Crit. Rev. Immunol. 19:389.
Rojas, A.I. & A.R. Ahmed (1999) Crit. Rev. Oral. Biol. Med. 10:337.
Hynes, R.O. (1999) Trends Cell. Biol. 9:M33.
Joseph-Silverstein, J. & R.L. Silverstein (1998) Cancer Invest. 16:176.
Fastbleep © 2019.