Desmoplakin is involved in organization of an adhesion complex in peripheral nerve regeneration after injury

• We studied the function of desmoplakin in the regeneration of peripheral nerves.
• Desmoplakin is upregulated in motoneurons after peripheral nerve injury in mice.
• Desmoplakin forms a complex with N-cadherin, plakoglobin and vimentin.
• Conditional ablation of desmoplakin in motoneurons impairs regeneration.
• Ablation of desmoplakin deteriorates cadherin localization and nerve outgrowth.

Peripheral nerves have the unique capability to regenerate after injury. Insights into regeneration of peripheral nerves after injury may have implications for neurodegenerative diseases of the nervous system. In this study, we analyzed the expression and function of desmoplakin in peripheral nerve regeneration. Desmoplakin was upregulated in spinal cord motoneurons after sciatic nerve injury. Conditional ablation of desmoplakin in motoneurons demonstrated that desmoplakin is necessary for normal motor regeneration. SiRNA and desmoplakin deletion-constructs revealed a role of desmoplakin in neurite extension in vitro. A complex of N-cadherin, plakoglobin, desmoplakin and vimentin was shown in motoneuronal cell cultures and peripheral nerves after injury in vivo. Motor nerve fiber regeneration and localization of N-cadherin and vimentin to axonal growth fronts were reduced in conditionally desmoplakin-ablated mice.These data indicate a function of desmoplakin in motor nerve regeneration by linking N-cadherin to intermediate filaments in regenerating motor axons.