CADHERIN
A Key Protein Plays Important Roles in Cell-Cell Adhesion
Introduction
CADHERIN
A Key Protein Plays Important Roles in Cell-Cell Adhesion
Introduction
Cadherins are a protein family of Ca2+-dependent transmembrane cell adhesion molecules that play important roles in cell morphogenesis, motility, wound healing, and the maintenance of organized tissues (see Ringwald 1994, Takeichi 1991 ). Currently known members in this family have been termed as B-, E-, N-, P-, T-, and Xenopus C-cadherins. The comparison of amino acid sequence has demontrated the homologs of these "calssical" cadherins as well as many other distantly related members, including desmocollins and desmogleins, which are proteins of the desmosomal dense plaque, and the Drosophila tumor suppressor gene fat (Buxton and Magee 1992, Kemler 1992).
The "classical" cadherins share a common modular structure. Their extracellular segments comprise five tandemly repeated similar domians of around 110 amino acids each, which have a folding topology that is like but not identical to that of immunoglobin variable-like domains (Overduin et al. 1995, Shapiro et al. 1995). Protocadherins also exist. They have many more tandemly repeated cadherin domains. Cadherins are normally anchored via their cytoplasmic region through catenins to cytoskeletal actin microfilaments. The interactions of cadherins with the action filament network in the cytoplasm and with other submembranous elements are regarded as the key functions in cell-cell adhesin. For instance, disruption of the interaction of the extracellular domains of E-cadherin ("E" referres to "Epithelial"; also known as "uvomorulin") on adjacent epithelial cells by chelation of Ca2+ alters cytoskeletal organization and leads to a loss of cadherin at the sites of cell-cell contact (Volberg et al. 1986, Volk and Geiger 1986). E-cadherin is also a tumor invasion suppressor whose function lost will induce many human carcinomas. For example, the gastric and endometrial tumor cells have been reported due to mutations and allelic deletions of E-cadherin gene (Oda et al. 1994, Risinger et al. 1994).
Here, the E-cadherin,
which has been well studied, will be mainly used as a model to introduce
and discuss the biological structure and functions of cadherins.
Since cadherins are transmembrane molecules, they contain two domains,
extracellular and cytoplasmic domains, respectively. At this time,
the researches of cytoplasmic domain foucs on the cadherin-catenin complex,
not itself simply. So, I will concentrate on the extracellular part
of cadherins, and only introduce the cytoplasmic part briefly. The
process of E-cadherin mediated cell adhesin will also be inroduced to represent
the major function of cadherins.
Introduction
Biological Structure & Functions
Process of E-cadherin Mediated Cell Adhesin
Information of Cadherins in PDB
By John A. Chen, Dept of
Entomology, Univ of Georgia, Athens, GA 30602-2603
Nov. 26,
2001