| First Author | Lewallen KA | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 8 | Pages | 3032-43 |
| PubMed ID | 21414924 | Mgi Jnum | J:169864 |
| Mgi Id | MGI:4943367 | Doi | 10.1523/JNEUROSCI.4345-10.2011 |
| Citation | Lewallen KA, et al. (2011) Assessing the role of the cadherin/catenin complex at the schwann cell-axon interface and in the initiation of myelination. J Neurosci 31(8):3032-43 |
| abstractText | Myelination is dependent on complex reciprocal interactions between the Schwann cell (SC) and axon. Recent evidence suggests that the SC-axon interface represents a membrane specialization essential for myelination; however, the manner in which this polarized-apical domain is generated remains a mystery. The cell adhesion molecule N-cadherin is enriched at the SC-axon interface and colocalizes with the polarity protein Par-3. The asymmetric localization is induced on SC-SC and SC-axon contact. Knockdown of N-cadherin in SCs cocultured with DRG neurons disrupts Par-3 localization and delays the initiation of myelination. However, knockdown or overexpression of neuronal N-cadherin does not influence the distribution of Par-3 or myelination, suggesting that homotypic interactions between SC and axonal N-cadherin are not essential for the events surrounding myelination. To further investigate the role of N-cadherin, mice displaying SC-specific gene ablation of N-cadherin were generated and characterized. Surprisingly, myelination is only slightly delayed, and mice are viable without any detectable myelination defects. beta-Catenin, a downstream effector of N-cadherin, colocalizes and coimmunoprecipitates with N-cadherin on the initiation of myelination. To determine whether beta-catenin mediates compensation on N-cadherin deletion, SC-specific gene ablation of beta-catenin was generated and characterized. Consistent with our hypothesis, myelination is more severely delayed than when manipulating N-cadherin alone, but without any defect to the myelin sheath. Together, our results suggest that N-cadherin interacts with beta-catenin in establishing SC polarity and the timely initiation of myelination, but they are nonessential components for the formation and maturation of the myelin sheath. |
