E-cadherin expression in postnatal Schwann cells is regulated by the cAMP-dependent protein kinase a pathway

• Published in: Glia Vol. 56; no. 15; pp. 1637 - 1647
• Main Authors: Crawford, Audrita T., Desai, Darshan, Gokina, Pradeepa, Basak, Sayantani, Kim, Haesun A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.11.2008
• Subjects: Animals; Animals, Newborn; autotypic junction; Axons - metabolism; cadherin switch; Cadherins - genetics; Cadherins - metabolism; Cell Communication - physiology; Cell Differentiation - physiology; Cell Membrane - metabolism; Cells, Cultured; Coculture Techniques; Cyclic AMP-Dependent Protein Kinases - genetics; Cyclic AMP-Dependent Protein Kinases - metabolism; Enzyme Activation - physiology; Ganglia, Spinal - cytology; Ganglia, Spinal - growth & development; Ganglia, Spinal - metabolism; N-cadherin; Peripheral Nerves - cytology; Peripheral Nerves - growth & development; Peripheral Nerves - metabolism; Rats; Rats, Sprague-Dawley; Schwann Cells - cytology; Schwann Cells - metabolism; Sensory Receptor Cells - cytology; Sensory Receptor Cells - metabolism; Signal Transduction - physiology
• DOI: 10.1002/glia.20716
• ISSN: 0894-1491

Expression of E‐cadherin in the peripheral nervous system is a highly regulated process that appears postnatally in concert with the development of myelinating Schwann cell lineage. As a major component of autotypic junctions, E‐cadherin plays an important role in maintaining the structural integrity of noncompact myelin regions. In vivo, the appearance of E‐cadherin in postnatal Schwann cell is accompanied by the disappearance of N‐cadherin, suggesting reciprocal regulation of the two cadherins during Schwann cell development. The molecular signal that regulates the cadherin switch in Schwann cell is unclear. Using a neuron‐Schwann cell co‐culture system, here we show that E‐cadherin expression is induced by components on the axonal membrane. We also show that the axonal effect is mediated through cAMP‐dependent protein kinase A (cAMP‐PKA) activation in the Schwann cell: (1) inhibition of cAMP‐PKA blocks axon‐induced E‐cadherin expression and (2) cAMP elevation in the Schwann cell is sufficient to induce E‐cadherin expression. In addition, cAMP‐dependent E‐cadherin expression is promoted by contact between adjacent Schwann cell membranes, suggesting its role in autotypic junction formation during myelination. Furthermore, cAMP‐induced E‐cadherin expression is accompanied by suppression of N‐cadherin expression. Therefore, we propose that axon‐dependent activation of cAMP‐PKA serves as a signal that promotes cadherin switch during postnatal development of Schwann cells. © 2008 Wiley‐Liss, Inc.