N-Cadherin

Cadherins are a superfamily of Ca2+-sensitive cell-cell adhesion molecules, which cause homophilic cell interactions. Cadherins can be divided into different subfamilies, namely, classical cadherins, desmosomal cadherins, protocadherins, and nonconventional cadherins (7TM cadherins, T-cadherin, FAT). Classical cadherins are often denoted by a prefix reflecting their principal expression domains e.g., E is epithelial, N is neuronal, and P is placental. However, this classification is not stringent, as for instance E-cadherin can also be found in certain neuronal tissues, and N-cadherin is also found in epithelial cells. Among the desmosomal cadherins, two subfamilies can be distinguished the desmocollins 1-3 and the desmogleins 1-4. 

The first cadherin to be expressed in the nervous system is N-cadherin 115... 

The classic cadherins are homophilic adhesion molecules. That is, E-cadherin expressed on one cell surface binds to E-cadherin expressed on an apposed cell surface, N-cadherin binds to N, P to P and so forth. It was originally thought that all cadherins would behave completely homophilically but it is now clear that, for example, N-cadherin can bind to R-cadherin, although perhaps more weakly than it would to N-cadherin. 

Tomaselli, K. J., Neugebauer, K. N., Bixby, J. L., Lilien, J. and Reichardt, L. F. N-cadherin and integrins two receptor systems that mediate neurite outgrowth on astrocyte surfaces. Neuron 1 33-43,1988. 

Matasunaga, M., Hatta, K., Nagafuchi, A. and Takeichi, M. Guidance of optic nerve fibers by N-cadherin adhesion molecules. Nature 334 62-64,1988. 

Inouye, A. and Sanes, J. R. Lamina-specific connectivity in the brain regulation by N-cadherin, neurotrophins, and glycoconjugates. Science 276 1428-1431,1997. 

Monier-Gavell, F. and Duban, J.-L. Cross talk between adhesion molecules control of N-cadherin activity by intracellular signals elicited by 01 and 03 integrins in migrating neural crest cells./. Cell Biol. 137 1663-1681,1997. 

Adhesion molecules such as LI, neural cell adhesion molecule (N-CAM) and N-cadherin promote axonal regeneration by homophilic interactions between axons and Schwann cell surfaces (see Ch. 7). The expression of p75 (low affinity NGF receptor, Ch. 27) is also increased at the Schwann cell surface after injury. Extracellular matrix molecules, such as tenascin and proteoglycans, increase the regenerative potential of damaged peripheral nerves by binding to integrins on the axonal surface. 

PSl forms a complex with p-catenin (CTNNBl), increasing P-catenin stability, and P-catenin levels are markedly reduced in the brains of AD patients with PSl mutations (157). One pathological characteristic of AD is extensive synapse loss. PSl is localized at the synapse, where it binds N-cadherin and modulates its adhesive activity. PSl is essential for efficient trafficking of N-cadherin from the ER to the plasma membrane. PW-mediated delivery of N-cadherin to the plasma membrane is important for N-cadherin to exert its physiological function, and it may control the state of cell-cell contact (158). 

Bruses JL (2011) N-cadherin regulates primary motor axon growth and branching during zebrafish embryonic development. J Comp Neurol 519 1797-1815... 

Silva AM, Liu-Gentry J, Dickey AS et al (2005) a-Latrotoxin increases spontaneous and depolarization-evoked exocytosis from pancreatic islet P-cells. J Physiol 565 783-99 Siu R, Fladd C, Rotin D (2006) N-cadherin is an in vivo substrate for PTPo and partidpates in PTPo-mediated inhibition of axon growth. Mol Cell Biol 27 208-19 Smith DS, Russell FE (1966) Structure of the venom gland of the black widow spider Latrodectus mactans. A preliminary light and electron microscopic study. In Russell FE, Saunders PR (eds) Animal Toxins, Oxford, Pergamon, pp 1-15... 

Blindt R, Bosserhoff AK, DammersJ, et al, Downregulation of N-cadherin in the neointima stimulates migration of smooth muscle cells by RhoA deactivation. Cardiovasc Res 2004 62( I) 212—222. 

Cadherins are calcium-dependent cell adhesion proteins that mainly participate in interactions with cadherins, located on other cells. Cadherins have five similar extracellular domains some of which have calcium-binding sites, and an intracellular C-terminal domain that interacts with the actin cytoskeleton. Different cadherins are named according to the tissues were they were first found. E-cadherins were found in many epithelial cells. N-cadherins are present in nerves and muscle and P-cadherin are present in placental cells. 

Marambaud P, Wen PH, Dutt A, Shioi J, Takashima A, Siman R, Robakis NK. A CBP binding transcriptional repressor produced by the PSl/epsilon-cleavage of N-cadherin is inhibited by PSl FAD mutations. Cell 2003 114 635-645. 

Fig. 6 Localization of key cardiac myocyte phenotypic markers of day 21 ECMs and BMSCs tube co-cultured in basal medium. Images demonstrate the expression of (a) sarcomeric myosin heavy chain (MF20), (b) cardiac troponin I, (c) a-actinin, (d) N-cadherin, (e) Gata4, (f) atrial natriuretic peptide (ANP), (g) desmin, and (h) connexin 43. Reproduced with permission from Valarmathi et al. [147]...

Cadherins are Ca -binding adhesion molecules that mediate homophilic interaction between cells. Cadherins are particularly important for selective fasciculation of regenerating axons. For instance, E-cadherin mediates attachment of unmyelinated sensory fibers and stabilizes glial network [42], and N-cadherin mediates axon-Schwann ceU interactions during regeneration [39, 43]. 

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