E-cadherin expression in postnatal Schwann cells is regulated by the cAMP-dependent protein kinase a pathway.
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.
Department of Biological Sciences, Rutgers University, Newark, New Jersey 07103, USA.
Audrita T
AT
Crawford
Darshan
D
Desai
Pradeepa
P
Gokina
Sayantani
S
Basak
Haesun A
HA
Kim
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D010525:Peripheral Nerves / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D015820:Cadherins; D017868:Cyclic AMP-Dependent Protein Kinases