title: Assessing the role of the cadherin/catenin complex at the Schwann cell-axon interface and in the initiation of myelination.
abstract: 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. β-Catenin, a downstream effector of N-cadherin, colocalizes and coimmunoprecipitates with N-cadherin on the initiation of myelination. To determine whether β-catenin mediates compensation on N-cadherin deletion, SC-specific gene ablation of β-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 β-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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lewallen
authors.forename: Yun-An A
authors.initials: YA
authors.lastname: Shen
authors.forename: Asia R
authors.initials: AR
authors.lastname: De la Torre
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Ng
authors.forename: Dies
authors.initials: D
authors.lastname: Meijer
authors.forename: Jonah R
authors.initials: JR
authors.lastname: Chan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D022001:Focal Adhesions / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology*; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*
chemical_list: D015820:Cadherins; C495268:Ctnnb1 protein, rat; D051176:beta Catenin