User:Maymi Myint/Cadherin

The cadherin family is essential in maintaining the cell to cell contact between each other and regulating for cytoskeletal complexes. Four types of cadherin molecules are classical cadherins, desmosomes, protocadherin, and atypical cadherins. Classical cadherins maintain the tone of tissues by forming a homodimer while desmosomes are the heterodimers. The intracellular portion of classical cadherins has regulatory proteins that helps the cadherins joining the actin cytoskeleton. Regulatory proteins include p-120 catenin, $$\alpha$$-catenin,  $$\beta$$-catenin, and vinculin. Binding of p-120 catenin and $$\beta$$-catenin to the homodimer increases the stability of the classical cadherin. $$\alpha$$-catenin is engaged by p120--catenin complex, where vinculin is recruited to take a role in indirect association with actin cytoskeleton. However, cadherin-catenin complex can also bind directly to the actin without the help of vinculin. Moreover, the strength of cadherin adhesion can increase by dephosphorylation of p120 catenin and the binding of $$\alpha$$-catenin and vinculin.

Classical cadherins exist in three forms, which are X-dimer, putative intermediate, and stand-swap dimer. X-dimer cadherins and stand-swap dimer cadherins conformations can be seen between two adhered cells. Two cadherins from the opposing cells connect each other by the exchange of tryptophan on the EC-1 domain in a trans conformation, and those cadherins are strand-swap cadherins. These strand-swap cadherins can be broken down into X-dimers without tryptophan exchange, but it does not disrupt the cell adhesion. X-dimer undergoes surface interactions between EC-1 and EC-2, forms the putative intermediate, then coverts into stand-swap dimer.

Although classical cadherins take a role in cell layer formation and structure formation, desmosomal cadherins focus on resisting the catastrophe towards the cells. Desmosomal cadherins are responsible to maintain the function of desmosomes that is to overturn the mechanical stress of the tissues. Similar to classical cadherins, desmosomal cadherins has a single transmembrane domain, five EC repeats, and an intracellular domain. Two types of desmosomal cadherins exist, and they are called desmogleins and desmocollins that contains an intracellular anchor and cadherin like sequence (ICS). The adaptor proteins that associate with desmosomal cadherins are plakoglobin (related to $$\beta$$-catenin), plakophilins (p120 catenin subfamily), and desmoplakins. The major function of desmoplakins to bind to intermediate filament thorough interaction with plakoglobin that attaches to ICS of desmogleins and desmocollins and plakophilins.

Atypical cadherins are different from other types of cadherins and consist of one or more extracellular repeat domains. The components that build an atypical cadherin are flamingo (seven pass transmembrane) and Dcad102F-like cadherins. Their job is to take part in signaling pathway instead of performing cell-cell adhesion.

N-cadherins have different functions that maintain the cell structure, cell-cell adhesion, internal adhesions. They participate greatly in keeping the ability of the structured heart due to pumping and release blood. Because of the contribution of N-cadherins adhering strongly between the cardiomyocytes, the heart can overcome the fracture, deformation, and fatigue that can result from the blood pressure. N-cadherin takes part in the development of the heart during embryo, especially in sorting out of the precardiac mesoderm. N-cadherins are robustly expressed in precardiac mesoderm, but they do not take a role in cardiac linage. An embryo with N-cadherin mutation still forms the primitive heart tube; however, N-cadherin deficient mice will have difficulties in maintaining the cardiomyocytes development. The myocytes of these mice will end up with dissociated myocytes surrounding the endocardial cell layer when they cannot preserve the cell adhesion due to the heart starting to pump. As a result, the cardiac outflow tract will be blocked causing cardiac swelling. By expressing either N-cadherin or E-cadherin, the heart will overcome the cell-adhesion defect proving that there is a transition between E-cadherins and N-cadherin, which is a process called epithelial migration transmission (EMT).